IBD & Intestinal Disorders

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Effective ways to combat harmful viruses, bacteria, fungi, and parasitic worms have driven major advances in medicine and contributed to a significant increase in human life expectancy over the past century. However, as knowledge about the role of these microorganisms in promoting and maintaining health deepens, there is a need for a new look at the impact of these treatments.

The list of drugs that can directly alter the gut microbiota is long. In addition to antibiotics, antivirals, antifungals, anthelmintics, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), laxatives, oral antidiabetics, antidepressants, antipsychotics, statins, chemotherapeutics, and immunosuppressants can trigger dysbiosis.

A 2020 study published in Nature Communications, which analyzed the impact of common medications on the composition and metabolic function of the gut bacteria, showed that of the 41 classes of medications, researchers found that 19 were associated with changes in the microbiome, most notably antibiotics, proton pump inhibitors, laxatives, and metformin.

“There are still no protocols aimed at preserving the microbiota during pharmacological treatment. Future research should identify biomarkers of drug-induced dysbiosis and potentially adapt live biotherapeutics to counteract it,” said Maria Júlia Segantini, MD, a coloproctologist at the University of São Paulo, Brazil.

 

Known Facts

Antibiotics, antivirals, antifungals, and anthelmintics eliminate pathogens but can also disrupt the microbiota across the gut, skin, mouth, lungs, and genitourinary tract.

“This ecosystem is part of the innate immune system and helps to balance inflammation and homeostasis. Loss of microbial diversity alters interspecies interactions and changes nutrient availability, which can undermine the ability to fend off pathogens,” said Segantini, noting the role of microbiota in vitamin K and B-complex production.

“The microbiome may lose its ability to prevent pathogens from taking hold. This is due to the loss of microbial diversity, changes in interactions between species, and the availability of nutrients,” she added.

Antibiotics, as is well known, eliminate bacterial species indiscriminately, reduce the presence of beneficial bacteria in the gut, and, therefore, favor the growth of opportunistic pathogenic microorganisms. However, in addition to their direct effects on microorganisms, different medications can alter the intestinal microbiota through various mechanisms linked to their specific actions. Here are some examples:

Proton pump inhibitors: These can facilitate the translocation of bacteria from the mouth to the intestine and affect the metabolic functions of the intestinal microbiota. “In users of these medications, there may be an enrichment of pathways related to carbohydrate metabolism, such as glycolysis and pyruvate metabolism, indicating possible changes in intestinal metabolism,” Segantini explained.

NSAIDs: NSAIDs can modify the function and composition of the intestinal microbiota, favor the growth of pathogenic species, and reduce the diversity of preexisting bacteria by reducing the presence of beneficial commensal bacteria, such as Lactobacillus and Bifidobacterium. “This is due to changes in the permeability of the intestinal wall, due to the inhibition of prostaglandins that help maintain the integrity of the intestinal barrier, enteropathy induced by NSAIDs, and drug interactions,” said Segantini.

Laxatives: Accelerated intestinal transit using laxatives impairs the quality of the microbiota and alters bile acid. Osmotic agents, such as lactulose and polyethylene glycol, may decrease resistance to infection.

“Studies in animal models indicate that polyethylene glycol can increase the proportion of Bacteroides and reduce the abundance of Bacteroidales bacteria, with lasting repercussions on the intestinal microbiota. Stimulant laxatives, in addition to causing an acceleration of the evacuation flow, can lead to a decrease in the production of short-chain fatty acids, which are important for intestinal health,” Segantini explained.

Chemotherapeutics: Chemotherapeutic agents can significantly influence the intestinal microbiota and affect its composition, diversity, and functionality, which in turn can affect the efficacy of treatment and the occurrence of adverse effects. “5-fluorouracil led to a decrease in the abundance of beneficial anaerobic genera, such as Blautia, and an increase in opportunistic pathogens, such as Staphylococcus and Escherichia coli, during chemotherapy. In addition, it can lead to an increase in the abundance of Bacteroidetes and Proteobacteria while reducing Firmicutes and Actinobacteria. These changes can affect the function of the intestinal barrier and the immune response. Other problems related to chemotherapy-induced dysbiosis are the adverse effects themselves, such as diarrhea and mucositis,” said Segantini.

Statins: Animal studies suggest that treatment with statins, including atorvastatin, may alter the composition of the gut microbiota. “These changes include the reduction of beneficial bacteria, such as Akkermansia muciniphila, and the increase in intestinal pathogens, resulting in intestinal dysbiosis. The use of statins can affect the diversity of the intestinal microbiota, although the results vary according to the type of statin and the clinical context.”

“Statins can activate intestinal nuclear receptors, such as pregnane X receptors, which modulate the expression of genes involved in bile metabolism and the inflammatory response. This activation can contribute to changes in the intestinal microbiota and associated metabolic processes. Although statins play a fundamental role in reducing cardiovascular risk, their interactions with the intestinal microbiota can influence the efficacy of treatment and the profile of adverse effects,” said Segantini.

Immunosuppressants: The use of immunosuppressants, such as corticosteroids, tacrolimus, and mycophenolate, has been associated with changes in the composition of the intestinal microbiota. “Immunosuppressant-induced dysbiosis can compromise the intestinal barrier, increase permeability, and facilitate bacterial translocation. This can result in opportunistic infections by pathogens and post-transplant complications, such as graft rejection and post-transplant diabetes,” Segantini stated.

“Alteration of the gut microbiota by immunosuppressants may influence the host’s immune response. For example, tacrolimus has been associated with an increase in the abundance of Allobaculum, Bacteroides, and Lactobacillus, in addition to elevated levels of regulatory T cells in the colonic mucosa and circulation, suggesting a role in modulating gut immunity,” she said.

Antipsychotics: Antipsychotics can affect gut microbiota in several ways, influencing bacterial composition and diversity, which may contribute to adverse metabolic and gastrointestinal effects.

“Olanzapine, for example, has been shown in rodent studies to increase the abundance of Firmicutes and reduce that of Bacteroidetes, resulting in a higher Firmicutes/Bacteroidetes ratio, which is associated with weight gain and dyslipidemia,” said Segantini.

She stated that risperidone increased the abundance of Firmicutes and decreased that of Bacteroidetes in animal models, correlating with weight gain and reduced basal metabolic rate. “Fecal transfer from risperidone-treated mice to naive mice resulted in decreased metabolic rate, suggesting that the gut microbiota would mediate these effects.”

Treatment with aripiprazole increased microbial diversity and the abundance of Clostridium, Peptoclostridium, Intestinibacter, and Christensenellaceae, in addition to promoting increased intestinal permeability in animal models.

“Therefore, the use of these medications can lead to metabolic changes, such as weight gain, hyperglycemia, dyslipidemia, and hypertension. This is due to a decrease in the production of short-chain fatty acids, which are important for maintaining the integrity of the intestinal barrier. Another change frequently observed in clinical practice is constipation induced by these medications. This functional change can also generate changes in the intestinal microbiota,” she said.

Oral antidiabetic agents: Oral antidiabetic agents influence the intestinal microbiota in different ways, depending on the therapeutic class. However, not all drug interactions in the microbiome are harmful. Liraglutide, a GLP-1 receptor agonist, promotes the growth of beneficial bacteria associated with metabolism.

“Exenatide, another GLP-1 agonist, has varied effects and can increase both beneficial and inflammatory bacteria,” explained Álvaro Delgado, MD, a gastroenterologist at Hospital Alemão Oswaldo Cruz in São Paulo, Brazil.

“In humans, an increase in bacteria such as Faecalibacterium prausnitzii has been observed, with positive effects. However, more studies are needed to evaluate the clinical impacts,” he said, and that, in animal models, these changes caused by GLP-1 agonists are linked to metabolic changes, such as greater glucose tolerance.

Metformin has been linked to increased abundance of A muciniphila, a beneficial bacterium that degrades mucin and produces short-chain fatty acids. “These bacteria are associated with improved insulin sensitivity and reduced inflammation,” he said.

Segantini stated that studies in mice have shown that vildagliptin also plays a positive role in altering the composition of the intestinal microbiota, increasing the abundance of Lactobacillus and Roseburia, and reducing Oscillibacter. “This same beneficial effect is seen with the use of sitagliptin,” she said.

Studies in animal models have also indicated that empagliflozin and dapagliflozin increase the populations of short-chain fatty acid-producing bacteria, such as Bacteroides and Odoribacter, and reduce the populations of lipopolysaccharide-producing bacteria, such as Oscillibacter.

“There are still not many studies regarding the use of sulfonylureas on the intestinal microbiota, so their action on the microbiota is still controversial,” said Segantini.

Antivirals: Antiviral treatment can influence gut microbiota in complex ways, depending on the type of infection and medication used.

“Although many studies focus on the effects of viral infection on the microbiota, there is evidence that antiviral treatment can also restore the healthy composition of the microbiota, promoting additional benefits to gut and immune health,” said Segantini.

In mice with chronic hepatitis B, entecavir restored the alpha diversity of the gut microbiota, which was reduced due to infection. In addition, the recovery of beneficial bacteria, such as Akkermansia and Blautia, was observed, which was associated with the protection of the intestinal barrier and reduction of hepatic inflammation.

Studies have indicated that tenofovir may aid in the recovery of intestinal dysbiosis induced by chronic hepatitis B virus infection and promote the restoration of a healthy microbial composition.

“Specifically, an increase in Collinsella and Bifidobacterium, bacteria associated with the production of short-chain fatty acids and modulation of the immune response, was observed,” said Segantini.

The use of antiretrovirals, such as lopinavir and ritonavir, has been associated with changes in the composition of the intestinal microbiota in patients living with HIV.

“A decrease in Lachnospira, Butyricicoccus, Oscillospira, and Prevotella, bacteria that produce short-chain fatty acids that are important in intestinal health and in modulating the immune response, was observed.”

Antifungals: As a side effect, antifungals also eliminate commensal fungi, which “share intestinal niches with microbiota bacteria, balancing their immunological functions. When modified, they culminate in dysbiosis, worsening of inflammatory pathologies — such as colitis and allergic diseases — and can increase bacterial translocation,” said Segantini. 

For example, fluconazole reduces the abundance of Candida spp. while promoting the growth of fungi such as Aspergillus, Wallemia, and Epicoccum.

“A relative increase in Firmicutes and Proteobacteria and a decrease in Bacteroidetes, Deferribacteres, Patescibacteria, and Tenericutes were also observed,” she explained.

Anthelmintics: These also affect the intestinal bacterial and fungal microbiota and alter the modulation of the immune response, in addition to having specific effects depending on the type of drug used.

 

Clinical Advice

Symptoms of dysbiosis include abdominal distension, flatulence, constipation or diarrhea, pain, fatigue, and mood swings. “The diagnosis is made based on the clinical picture, since tests such as small intestinal bacterial overgrowth, which indicate metabolites of bacteria associated with dysbiosis, specific stool tests, and microbiota mapping with GI-MAP [Gastrointestinal Microbial Assay Plus], for example, are expensive, difficult to access, and often inconclusive for diagnosis and for assessing the cause of the microbiota alteration,” explained Fernando Seefelder Flaquer, MD, a gastroenterologist at Albert Einstein Israelite Hospital in São Paulo.

When caused by medication, dysbiosis tends to be reversed naturally after discontinuation of the drug. “However, in medications with a high chance of altering the microbiota, probiotics can be used as prevention,” said Flaquer.

“To avoid problems, it is important to use antibiotics with caution and prefer, when possible, those with a reduced spectrum,” advised Delgado.

“Supplementation with probiotics and prebiotics can help maintain the balance of the microbiota, but it should be evaluated on a case-by-case basis, as its indications are still restricted at present.”

Currently, dysbiosis management relies on nutritional support and lifestyle modifications. “Physical exercise, management of psychological changes, and use of probiotics and prebiotics. In specific cases, individualized treatment may even require the administration of some types of antibiotics,” explained Segantini.

Although fecal microbiota transplantation (FMT) has been widely discussed and increasingly studied, it should still be approached with caution. While promising, FMT remains experimental for most conditions, and its use outside research settings should be carefully considered, particularly in patients who are immunocompromised or have compromised intestinal barriers.

“Currently, the treatment has stood out as promising for cases of recurrent Clostridioides difficile infection, being the only consolidated clinical indication,” said Segantini.

 

Science Hype

The interest in gut microbiome research has undoubtedly driven important scientific advances, but it also risks exaggeration. While the field holds enormous promise, much of the research remains in its early stages.

“The indiscriminate use of probiotics and reliance on microbiota analysis tests for personalized probiotic prescriptions are growing concerns,” Delgado warned. “We need to bridge the gap between basic science and clinical application. When that translation happens, it could revolutionize care for many diseases.”

Flaquer emphasized a broader issue: “There has been an overvaluation of dysbiosis and microbiota-focused treatments as cure-alls for a wide range of conditions — often subjective or lacking solid scientific correlation — such as depression, anxiety, fatigue, cancer, and even autism.”

With ongoing advances in microbiome research, understanding the impact of this complex ecosystem on human health has become essential across all medical specialties. In pediatrics, for instance, microbiota plays a critical role in immune and metabolic development, particularly in preventing conditions such as allergies and obesity.

In digestive surgery, preoperative use of probiotics has been shown to reduce complications and enhance postoperative recovery. Neurological research has highlighted the gut-brain axis as a potential factor in the development of neurodegenerative diseases. In gynecology, regulating the vaginal microbiota is key to preventing infections and complications during pregnancy.

“Given the connections between the microbiota and both intestinal and systemic diseases, every medical specialist should understand how it relates to the conditions they treat daily,” concluded Flaquer.

This story was translated from Medscape’s Portuguese edition.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Antibiotic treatment while awaiting appendectomy does not lower risk for appendiceal perforation in patients with uncomplicated acute appendicitis, according to a new study.

While the percentage of surgical site infections (SSIs) was small for both groups, patients who received antibiotics during the waiting period had lower rates of these infections.

The trial — titled PERFECT-Antibiotics — was a substudy embedded in a larger PERFECT clinical trial, which aimed to determine whether an in-hospital delay of appendectomy resulted in increased risk for appendiceal perforation when compared to emergent surgery.

The trial “concluded that appendectomy does not need to be performed promptly in acute uncomplicated appendicitis and can be scheduled within 24 hours without increasing complications,” senior author Panu Mentula, MD, of the Department of Gastroenterological Surgery, Helsinki University Hospital, Helsinki, Finland, and colleagues wrote in the study. “The next question is whether preoperatively started antibiotic treatment reduces the risk of appendiceal perforations.”

The findings were published online in JAMA Surgery on May 14, 2025.

 

Trial Design

PERFECT-Antibiotics was an open-label, randomized trial conducted at two hospitals in Finland and one hospital in Norway. Researchers enrolled 1774 individuals diagnosed with acute uncomplicated appendicitis, diagnosed clinically or via imaging. Patients were placed in one of two groups: The antibiotic group received intravenous (IV) cefuroxime (1500 mg) and metronidazole (500 mg) every 8 hours until surgery, while the nonantibiotic group waited for surgery without antibiotics.

All patients received one dose of IV cefuroxime (1500 mg) and metronidazole (500 mg) during anesthesia induction. The primary outcome was perforated appendicitis and secondary outcomes included complication rate and SSIs within 30 days of follow-up.

The median age of patients was 35 years (interquartile range [IQR], 28-46 years), and 55% of patients were men. Patients waited a median time of 9 hours (IQR, 4.3-15.5) from study randomization to undergoing surgery.

 

No Difference in Appendiceal Perforation

Of the 888 patients in the preoperative antibiotic group, 26.2% received one dose, 38.7% received two doses, 22.6% received three doses, and 11.8% received four or more doses of antibiotics, including the antibiotic dose given during anesthesia. A total of 74 patients (8.3%) in this group had a perforated appendix.

Of the 886 patients not given preoperative antibiotics, 79 (8.9%) had a perforated appendix, which met the predetermined noninferiority threshold.

The groups had similar complication rates over the 30-day follow-up, though SSIs were lower in the antibiotic group (1.6%) than the no antibiotic group (3.2%).

The researchers estimated that the number needed to treat for antibiotic therapy was 63 for SSIs, 83 for intra-abdominal SSI, and 125 for reintervention.

“Although longer preoperative antibiotic treatment resulted in slightly lower rate of postoperative infectious complications, the actual difference was very small and probably clinically not significant to justify longer preoperative antibiotic treatment,” Mentula and colleagues wrote.

 

Lower Infection Rates With Antibiotics

Commenting on the study for GI & Hepatology News, Theodore Pappas, MD, professor of surgery at Duke University School of Medicine in Durham, North Carolina, placed greater importance on these secondary outcomes.

Intra-abdominal infections, a subset of SSIs, were more than twice as common in the no-antibiotic group (1.9%) than in the antibiotic group (0.7%; P = .02). Positive blood cultures were also more common in the no-antibiotic group than the antibiotic group (P = .02).

While the authors qualified these results, “the reality was it was better to use antibiotics,” he said.

There was also a “big overlap between the two groups,” he said, which may have muted differences between the two groups. For example, one fourth of patients in the antibiotic group received only one dose of antibiotics, the same treatment regimen as the no-antibiotic group.

“Although protocol required prophylaxis in all patients in the induction of anesthesia, some clinicians thought that it was unnecessary, because antibiotics had already been given only a couple of hours ago” in patients in the antibiotic group, Mentula told GI & Hepatology News. She did not think that would affect the study’s results.

The PERFECT trial and the antibiotics subtrial answer two important questions that have been asked for years, Pappas continued: Whether appendectomy for uncomplicated acute appendicitis needs to be performed emergently and if antibiotics administered while waiting for surgery improve outcomes.

“Basically, the study shows that you probably should keep them on antibiotics while you’re waiting,” he said.

The study was funded by Finnish Medical Foundation, the Mary and Georg Ehrnrooth Foundation, the Biomedicum Helsinki Foundation, and The Norwegian Surveillance Programme for Antimicrobial Resistance and research funds from the Finnish government. Mentula received grants from the Finnish government during the conduct of the study and personal fees from Pfizer outside the submitted work. Pappas reported no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study adds to what has been emerging in the literature — namely that there appear to be gut microbiome “signatures” for various pain conditions — suggesting that microbiome-based diagnostics and therapeutics may one day be routine for a broad range of pain conditions.

“There is now a whole list of pain conditions that appear to have these signatures, including postoperative pain, arthritis, neuropathy and migraine to name a few,” Robert Bonakdar, MD, director of pain management, Scripps Center for Integrative Medicine, San Diego, told GI & Hepatology News.

Fibromyalgia and complex regional pain syndrome (CRPS) are also on the list.

A team led by Amir Minerbi, MD, PhD, director of the Institute for Pain Medicine, Haifa, Israel, and colleagues published one of the first articles on gut changes in fibromyalgia. They noted that the gut microbiome could be utilized to determine which individuals had the condition and which did not — with about a 90% accuracy.

The team went on to show that transplanting gut microbiota from patients with fibromyalgia into germ-free mice was sufficient to induce pain-like behaviors in the animals — “effects that were reversed when healthy human microbiota were transplanted instead,” Minerbi told GI & Hepatology News.

Further, in a pilot clinical study, the researchers showed that transplanting microbiota from healthy donors led to a reduction in pain and other symptoms in women with treatment-resistant fibromyalgia.

Most recently, they found significant differences in the composition of the gut microbiome in a cohort of patients with CRPS from Israel, compared to matched pain-free control individuals.

Notably, two species — Dialister succinatiphilus and Phascolarctobacterium faecium – were enriched in patients with CRPS, while three species — Ligilactobacillus salivarius, Bifidobacterium dentium, and Bifidobacterium adolescentis – were increased in control samples, according to their report published last month in Anesthesiology.

“Importantly,” these findings were replicated in an independent cohort of patients with CRPS from Canada, “suggesting that the observed microbiome signature is robust and consistent across different environments,” Minerbi told GI & Hepatology News.

 

Causal Role? 

“These findings collectively suggest a causal role for the gut microbiome in at least some chronic pain conditions,” Minerbi said.

However, the co-authors of a linked editorial cautioned that it’s “unclear if D succinatiphilus or P faecium are functionally relevant to CRPS pathophysiology or if the bacteria increased in healthy control samples protect against CRPS development.”

Minerbi and colleagues also observed that fecal concentrations of all measured short chain fatty acids (SCFA) in patients with CRPS were lower on average compared to pain-free control individuals, of which butyric, hexanoic, and valeric acid showed significant depletion.

Additionally, plasma concentrations of acetic acid showed significant depletion in patients with CRPS vs control individuals, while propionate, butyrate, isobutyrate and 2-methyl-butyric acid showed a trend toward lower concentrations.

The quantification of SCFA in patient stool and serum is a “notable advance” in this study, Zulmary Manjarres, PhD; Ashley Plumb, PhD; and Katelyn Sadler, PhD; with the Center for Advanced Pain Studies at The University of Texas at Dallas, wrote in their editorial.

SCFA are produced by bacteria as a byproduct of dietary fiber fermentation and appropriate levels of these compounds are important to maintain low levels of inflammation in the colon and overall gut health, they explained.

This begs the question of whether administering probiotic bacteria — many of which are believed to exert health benefits through SCFA production — can be used to treat CRPS-associated pain. It’s something that needs to be studied, the editorialists wrote.

Yet, in their view, the “most notable achievement” of Minerbi and colleagues is the development of a machine learning model that accurately, specifically and sensitively categorized individuals as patients with CRPS or control individuals based on their fecal microbiome signature.

The model, trained on exact sequence variant data from the Israeli patients, achieved 89.5% accuracy, 90.0% sensitivity, and 88.9% specificity in distinguishing patients with CRPS from control individuals in the Canadian cohort.

Interestingly, in three patients with CRPS who underwent limb amputation and recovered from their pain, their gut microbiome signature remained unchanged, suggesting that microbiome alterations might precede or persist beyond symptomatic phases.

 

Test and Treat: Are We There Yet? 

The gut microbiome link to chronic pain syndromes is a hot area of research, but for now gut microbial testing followed by treatment aimed at “fixing” the microbiome remains largely experimental.

At this point, comprehensive gut-microbiome sequencing is not a routine, guideline-supported part of care for fibromyalgia or any chronic pain condition.

“Unfortunately, even for doctors interested in this area, we are not quite at the state of being able to diagnose and treat pain syndrome based on microbiome data,” Bonakdar told GI & Hepatology News.

He said there are many reasons for this including that this type of microbiome analysis is not commonly available at a routine lab. If patients do obtain testing, then the results are quite complex and may not translate to a diagnosis or a simple microbiome intervention.

“I think the closest option we have now is considering supplementing with commonly beneficial probiotic in pain conditions,” Bonakdar said.

One example is a preliminary fibromyalgia trial which found that supplementing with Lactobacillus, Bifidobacterium, and Saccharomyces boulardii appeared to have benefit.

“Unfortunately, this is hit or miss as other trials such as one in low back pain did not find benefit,” Bonakdar said.

Addressing gut microbiome changes will become “more actionable when microbiome analysis is more commonplace as well as is the ability to tailor treatment to the abnormalities seen on testing in a real-world manner,” Bonakdar said.

“Until then, there is no harm in promoting an anti-inflammatory diet for our patients with pain which we know can improve components of the microbiome while also supporting pain management,” he concluded.

Minerbi, Bonakdar, and the editorial writers had no relevant disclosures.

A version of this article appeared on Medscape.com.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.

Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.

Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.

Small Bowel

Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.

Colon

Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.

Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.

Inflammatory Bowel Disease

Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.

Pancreas

Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.

Hepatology

Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.

Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.

Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.

Miscellaneous

Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.

Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.

Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.

Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.

Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.

Small Bowel

Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.

Colon

Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.

Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.

Inflammatory Bowel Disease

Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.

Pancreas

Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.

Hepatology

Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.

Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.

Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.

Miscellaneous

Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.

Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.

Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Below are some selections from what I am reading in the AGA journals, highlighting clinically applicable and possibly practice-changing expert reviews and studies.

Esophagus/Motility

Carlson DA, et al. A Standardized Approach to Performing and Interpreting Functional Lumen Imaging Probe Panometry for Esophageal Motility Disorders: The Dallas Consensus. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.234.

Parkman HP, et al; NIDDK Gastroparesis Clinical Research Consortium. Characterization of Patients with Symptoms of Gastroparesis Having Frequent Emergency Department Visits and Hospitalizations. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.033.

Dellon ES, et al. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Feb. doi: 10.1016/j.cgh.2024.12.024.

Small Bowel

Hård Af Segerstad EM, et al; TEDDY Study Group. Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study. Gastroenterology. 2025 Feb. doi: 10.1053/j.gastro.2025.01.241.

Colon

Shaukat A, et al. AGA Clinical Practice Update on Current Role of Blood Tests for Colorectal Cancer Screening: Commentary. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.04.003.

Bergman D, et al. Cholecystectomy is a Risk Factor for Microscopic Colitis: A Nationwide Population-based Matched Case Control Study. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2024.12.032.

Inflammatory Bowel Disease

Ben-Horin S, et al; Israeli IBD Research Nucleus (IIRN). Capsule Endoscopy-Guided Proactive Treat-to-Target Versus Continued Standard Care in Patients With Quiescent Crohn’s Disease: A Randomized Controlled Trial. Gastroenterology. 2025 Mar. doi: 10.1053/j.gastro.2025.02.031.

Pancreas

Guilabert L, et al; ERICA Consortium. Impact of Fluid Therapy in the Emergency Department in Acute Pancreatitis: a posthoc analysis of the WATERFALL Trial. Clin Gastroenterol Hepatol. 2025 Apr. doi: 10.1016/j.cgh.2025.01.038.

Hepatology

Rhee H, et al. Noncontrast Magnetic Resonance Imaging vs Ultrasonography for Hepatocellular Carcinoma Surveillance: A Randomized, Single-Center Trial. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2024.12.035.

Kronsten VT, et al. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025 Jan. doi: 10.1053/j.gastro.2025.01.010.

Edelson JC, et al. Accuracy and Safety of Endoscopic Ultrasound–Guided Liver Biopsy in Patients with Metabolic Dysfunction–Associated Liver Disease. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250918.

Miscellaneous

Martin J, et al. Practical and Impactful Tips for Private Industry Collaborations with Gastroenterology Practices. Clin Gastroenterol Hepatol. 2025 Mar. doi: 10.1016/j.cgh.2025.01.021.

Tejada, Natalia et al. Glucagon-like Peptide-1 Receptor Agonists Are Not Associated With Increased Incidence of Pneumonia After Endoscopic Procedures. Tech Innov Gastrointest Endosc. 2025 Apr. doi: 10.1016/j.tige.2025.250925.

Lazaridis KN, et al. Microplastics and Nanoplastics and the Digestive System. Gastro Hep Adv. 2025 May. doi: 10.1016/j.gastha.2025.100694.

Dr. Trieu is assistant professor of medicine, interventional endoscopy, in the Division of Gastroenterology at Washington University in St. Louis School of Medicine, Missouri.

Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Dear colleagues,

Lower gastrointestinal bleeding (LGIB) remains a frequent and sometimes perplexing clinical challenge. Despite advancements in endoscopic and radiologic tools, questions persist: What is the role and optimal timing of colonoscopy? How can we best utilize radiologic studies like CTA or tagged RBC scans? How should we manage patients with recurrent or intermittent bleeding that defies localization?

In this issue of Perspectives, Dr. David Wan, Dr. Fredella Lee, and Dr. Zeyad Metwalli offer their expert insights on these difficult questions. Dr. Wan, drawing on over 15 years of experience as a GI hospitalist, shares – along with his coauthor Dr. Lee – a pragmatic approach to LGIB based on clinical patterns, evolving data, and multidisciplinary collaboration. Dr. Metwalli provides the interventional radiologist’s perspective, highlighting how angiographic techniques can complement GI management and introducing novel IR strategies for patients with recurrent or elusive bleeding.

We hope their perspectives will offer valuable guidance for your practice. Join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Management of Lower Gastrointestinal Bleeds: GI Perspective

BY FREDELLA LEE, MD; DAVID WAN, MD

 

Acute lower gastrointestinal bleeding (LGIB) presents unique challenges. Much of this stems from the natural history of diverticular bleeding, the most common etiology of LGIB.

First, while bleeding can be severe, most will spontaneously stop. Second, despite our best efforts with imaging or colonoscopy, finding an intervenable lesion is rare. Third, LGIB has significant rates of rebleeding that are unpredictable.

While serving as a GI hospitalist for 15 years and after managing over 300 cases of LGIB, I often find myself frustrated and colonoscopy feels futile. So how can we rationally approach these patients? We will focus on three clinical questions to develop a framework for LGIB management.

• What is the role and timing for a colonoscopy?
• How do we best utilize radiologic tests?
• How can we prevent recurrent LGIB?

The Role of Colonoscopy

Traditionally, colonoscopy within 24 hours of presentation was recommended. This was based on retrospective cohort data showing higher endoscopic intervention rates and better clinical outcomes. However, this protocol requires patients to drink a significant volume of bowel preparation over a few hours (often requiring an NGT) to achieve clear rectal effluent. Moreover, one needs to mobilize a team (i.e., nurse, technician, anesthesiologist, and gastroenterologist), and find an appropriate location to scope (i.e., ED, ICU, or OR), Understandably, this is challenging, especially overnight. When the therapeutic yield is relatively low, this approach quickly loses enthusiasm.

Importantly, meta-analyses of the randomized controlled trials, have shown that urgent colonoscopies (<24 hours upon presentation), compared to elective colonoscopies (>24 hours upon presentation), do not improve clinical outcomes such as re-bleeding rates, transfusion requirements, mortality, or length of stay. In these studies, the endoscopic intervention rates were 17-34%, however, observational data shows rates of only 8%. In our practice, we will use a clear cap attachment device and water jet irrigation to increase the odds of detecting an active source of bleeding. Colonoscopy has a diagnostic yield of 95% – despite its low therapeutic yield; and while diverticular bleeds constitute up to 64% of cases, one does not want to miss colorectal cancer or other diagnoses. Regardless, there is generally no urgency to perform a colonoscopy. To quote a colleague, Dr. Elizabeth Ross, “there is no such thing as door-to-butt time.”

The Role of Radiology

Given the limits of colonoscopy, can radiographic tests such as computed tomography angiography (CTA) or tagged red blood cell (RBC) scan be helpful? Multiple studies have suggested using CTA as the initial diagnostic test. The advantages of CTAs are:

• Fast, readily available, and does not require a bowel preparation
• If negative, CTAs portend a good prognosis and make it highly unlikely to detect active extravasation on visceral angiography
• If positive, can localize the source of bleed and increase the success of intervention

Whether a positive CTA should be followed with a colonoscopy or visceral angiography remains unclear. Studies show that positive CTAs increase the detection rate of stigmata of recent hemorrhage on colonoscopy. Positive CTAs can also identify a target for embolization by interventional radiology (IR). Though an important caveat is that the success rate of embolization is highest when performed within 90 minutes of a positive CTA. This highlights that if you have IR availability, it is critical to have clear communication, a well-defined protocol, and collaboration among disciplines (i.e., ED, medical team, GI, and IR).

At our institution, we have implemented a CTA-guided protocol for severe LGIB. Those with positive CTAs are referred immediately to IR for embolization. If the embolization is unsuccessful or CTA is negative, the patient will be planned for a non-urgent inpatient colonoscopy. However, our unpublished data and other studies have shown that the overall CTA positivity rates are only between 16-22%. Moreover, one randomized controlled trial comparing CTA versus colonoscopy as an initial test did not show any meaningful difference in clinical outcomes. Thus, the benefit of CTA and the best approach to positive CTAs remains in question.

Lastly, people often ask about the utility of RBC nuclear scans. While they can detect bleeds at a slower rate (as low as 0.1 mL/min) compared to CTA (at least 0.4 mL/min), there are many limitations. RBC scans take time, are not available 24-7, and cannot precisely localize the site of bleeding. Therefore, we rarely recommend them for LGIB.

 

Approach to Recurrent Diverticular Bleeding

Unfortunately, diverticular bleeding recurs in the hospital 14% of the time and up to 25% at 5 years. When this occurs, is it worthwhile to repeat another colonoscopy or CTA?

Given the lack of clear data, we have adopted a shared decision-making framework with patients. Oftentimes, these patients are older and have significant co-morbidities, and undergoing bowel preparation, anesthesia, and colonoscopy is not trivial. If the patient is stable and prior work-up has excluded pertinent alternative diagnoses other than diverticular bleeding, then we tell patients the chance of finding an intervenable lesion is low and opt for conservative management. Meanwhile, if the patient has persistent, hemodynamically significant bleeding, we recommend a CTA based on the rationale discussed previously.

The most important clinical decision may not be about scoping or obtaining a CTA – it is medication management. If they are taking NSAIDs, they should be discontinued. If antiplatelet or anticoagulation agents were held, they should be restarted promptly in individuals with significant thrombotic risk given studies showing that while rebleeding rates may increase, overall mortality decreases.

In summary, managing LGIB and altering its natural history with either endoscopic or radiographic means is challenging. More studies are needed to guide the optimal approach. Reassuringly, most bleeding self-resolves and patients have good clinical outcomes.

Dr. Lee is a resident physician at New York Presbyterian Weill Cornell Medical Center, New York, NY. Dr. Wan is associate professor of clinical medicine at Weill Cornell Medicine, New York, N.Y. They declare no conflicts of interest.

Lower Gastrointestinal Bleeding: An Interventional Radiologist’s Perspective

BY ZEYAD METWALLI, MD, FSIR

 

When colonoscopy fails to localize and/or stop lower gastrointestinal bleeding (LGIB), catheter angiography has been commonly employed as a tool for both diagnosis and treatment of bleeding with embolization. Nuclear medicine or CT imaging studies can serve as useful adjuncts for confirming active bleeding and localizing the site of bleeding prior to angiography, particularly if this information is not provided by colonoscopy. Provocative mesenteric angiography has also become increasingly popular as a troubleshooting technique in patients with initially negative angiography.

Localization of Lower Gastrointestinal Bleeding

Radionuclide technetium-99m-lableled red blood cell scintigraphy (RBCS), also known as tagged RBC scintigraphy, has been in use since the early 1980s for investigation of acute gastrointestinal bleeding. RBCS has a high sensitivity for detection of active bleeding with a theoretical ability to detect bleeding at rates as low as 0.04-0.2 mL/minute.

Imaging protocols vary but should include dynamic images, which may aid in localization of bleeding. The relatively long half-life of the tracer used for imaging allows for delayed imaging 12 to 24 hours after injection. This can be useful to confirm active bleeding, particularly when bleeding is intermittent and is not visible on initial images. 

With the advent of computed tomography angiography (CTA), which continues to increase in speed, imaging quality and availability, the use of RBCS for evaluation of LGIB has declined. CTA is quicker to perform than RBCS and allows for detection of bleeding as well as accurate anatomic localization, which can guide interventions.

CTA provides a more comprehensive anatomic evaluation, which can aid in the diagnosis of a wide variety of intra-abdominal issues. Conversely, CTA may be less sensitive than RBCS for detection of slower acute bleeding, detecting bleeding at rates of 0.1-1 mL/min. In addition, intermittent bleeding which has temporarily stopped at the time of CTA may evade detection.

Lastly, CTA may not be appropriate in patients with impaired renal function due to risk of contrast-induced nephropathy, particularly in patients with acute kidney injury, which commonly afflicts hospitalized patients with LGIB. Prophylaxis with normal saline hydration should be employed aggressively in patients with impaired renal function, particularly when eGFR is less than 30 mL/minute. Iodinated contrast should be used judiciously in these patients.

In clinical practice, CTA and RBCS have a similar ability to confirm the presence or absence of clinically significant active gastrointestinal bleeding. Given the greater ability to rapidly localize the bleeding site with CTA, this is generally preferred over RBCS unless there is a contraindication to performing CTA, such as severe contrast allergy or high risk for development of contrast-induced nephropathy.

 

Role of Catheter Angiography and Embolization

Mesenteric angiography is a well-established technique for both detection and treatment of LGIB. Hemodynamic instability and need for packed RBC transfusion increases the likelihood of positive angiography. Limitations include reduced sensitivity for detection of bleeding slower than 0.5-1 mL/minute as well as the intermittent nature of LGIB, which will often resolve spontaneously. Angiography is variably successful in the literature with a diagnostic yield between 40-80%, which encompasses the rate of success in my own practice.

Once bleeding is identified, microcatheter placement within the feeding vessel as close as possible to the site of bleeding is important to ensure treatment efficacy and to limit risk of complications such as non-target embolization and bowel ischemia. Once the feeding vessel is selected with a microcatheter, embolization can be accomplished with a wide variety of tools including metallic coils, liquid embolic agents, and particles. In the treatment of LGIB, liquid embolic agents (e.g., n-butyl cyanoacrylate or NBCA, ethylene vinyl alcohol copolymer, etc.) and particles should be used judiciously as distal penetration increases the risk of bowel ischemia and procedure-related morbidity. For this reason, metallic coils are often preferred in the treatment of LGIB.

Although the source of bleeding is variable and may include diverticulosis, recent polypectomy, ulcer, tumor or angiodysplasia, the techniques employed are similar. Accurate and distal microcatheter selection is a key driver for successful embolization and minimizing the risk of bowel ischemia. Small intestinal bleeds can be challenging to treat due to the redundant supply of the arterial arcades supplying small bowel and may require occlusion of several branches to achieve hemostasis. This approach must be balanced with the risk of developing ischemia after embolization. Angiodysplasia, a less frequently encountered culprit of LGIB, may also be managed with selective embolization with many reports of successful treatment with liquid embolic agents such as NBCA mixed with ethiodized oil.

 

Provocative Mesenteric Angiography for Occult Bleeding

When initial angiography in a patient with suspected active LGIB is negative, provocative angiography can be considered to uncover an intermittent bleed. This may be particularly helpful in a patient where active bleeding is confirmed on a prior diagnostic test.

The approach to provocative mesenteric angiography varies by center, and a variety of agents have been used to provoke bleeding including heparin, vasodilators (i.e., nitroglycerin, verapamil, etc.) and thrombolytics (i.e., tPA), often in combination. Thrombolytics can be administered directly into the territory of interest (i.e., superior mesenteric or inferior mesenteric artery) while heparin may be administered systemically or directly into the catheterized artery. Reported success rates for provoking angiographically visible bleeding vary, but most larger series report a 40-50% success rate. The newly detected bleeding can then be treated with either embolization or surgery. A surgeon should be involved and available when provocative angiography is planned should bleeding fail to be controlled by embolization.

In summary, when colonoscopy fails to identify or control lower gastrointestinal bleeding (LGIB), imaging techniques such as RBCS and CTA play a crucial role in localizing active bleeding. While RBCS is highly sensitive, especially for intermittent or slow bleeding, CTA offers faster, more detailed anatomical information and is typically preferred unless contraindicated by renal issues or contrast allergies. Catheter-based mesenteric angiography is a well-established method for both diagnosing and treating LGIB, often using metallic coils to minimize complications like bowel ischemia. In cases where initial angiography is negative, provocative angiography – using agents like heparin or thrombolytics – may help unmask intermittent bleeding, allowing for targeted embolization or surgical intervention.

Dr. Metwalli is associate professor in the Department of Interventional Radiology, Division of Diagnostic Imaging, at The University of Texas MD Anderson Cancer Center, Houston, Texas. He declares no conflicts of interest.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

Introduction: Cases

Patient 1: A 57-year-old man with post-prandial distress variant functional dyspepsia (FD) was recommended to start nortriptyline. He previously established primary care with a physician he met at a barbershop health fair in Harlem, who referred him for specialty evaluation. Today, he presents for follow-up and reports he did not take this medication because he heard it is an antidepressant. How would you counsel him? 

Patient 2: A 61-year-old woman was previously diagnosed with mixed variant irritable bowel syndrome (IBS-M). Her symptoms have not significantly changed. Her prior workup has been reassuring and consistent with IBS-M. Despite this, the patient pushes to repeat a colonoscopy, fearful that something is being missed or that she is not being offered care because of her undocumented status. How do you respond? 

Patient 3: A 36-year-old man is followed for the management of generalized anxiety disorder and functional heartburn. He was started on low-dose amitriptyline with some benefit, but follow-up has been sporadic. On further discussion, he reports financial stressors, time barriers, and difficulty scheduling a meeting with his union representative for work accommodations as he lives in a more rural community. How do you reply?

Patient 4: A 74-year-old man with Parkinson’s disease who uses a wheelchair has functional constipation that is well controlled on his current regimen. He has never undergone colon cancer screening. He occasionally notices blood in his stool, so a colonoscopy was recommended to confirm that his hematochezia reflects functional constipation complicated by hemorrhoids. He is concerned about the bowel preparation required for a colonoscopy given his limited mobility, as his insurance does not cover assistance at home. He does not have family members to help him. How can you assist him?

Social determinants of health, health disparities, and DGBIs

Social determinants of health affect all aspects of patient care, with an increasing body of published work looking at potential disparities in organ-based and structural diseases.^1,2,3,4 However, little has been done to explore their influence on disorders of gut-brain interaction or DGBIs.

From a pathophysiologic perspective, the impact of biopsychosocial stressors is particularly relevant in patients with DGBIs. As DGBIs cannot be diagnosed with a single laboratory or endoscopic test, the patient history is of the utmost importance and physician-patient rapport is paramount in their treatment. Such rapport may be more difficult to establish in patients coming from historically marginalized and minoritized communities who may be distrustful of healthcare as an institution of (discriminatory) power. 

 

Potential DGBI management pitfalls in historically marginalized or minoritized communities

For racial and ethnic minorities in the United States, disparities in healthcare take on many forms. People from racial and ethnic minority communities are less likely to receive a gastroenterology consultation and those with IBS are more likely to undergo procedures as compared to White patients with IBS.⁶ Implicit bias may lead to fewer specialist referrals, and specialty care may be limited or unavailable in some areas. Patients may prefer seeing providers in their own community, with whom they share racial or ethnic identities, which could lead to fewer referrals to specialists outside of the community.

Historical discrimination contributes to a lack of trust in healthcare professionals, which may lead patients to favor more objective diagnostics such as endoscopy or view being counseled against invasive procedures as having necessary care denied. Due to a broader cultural stigma surrounding mental illness, patients may be more hesitant to utilize neuromodulators, which have historically been used for psychiatric diagnoses, as it may lead them to conflate their GI illness with mental illness.^7,8

Since DGBIs cannot be diagnosed with a single test or managed with a single treatment modality, providing excellent care for patients with DGBIs requires clear communication. For patients with limited English proficiency (LEP), access to high-quality language assistance is the foundation of comprehensive care. Interpreter use (or lack thereof) may limit the ability to obtain a complete and accurate clinical history, which can lead to fewer referrals to specialists and increased reliance on endoscopic evaluations that may not be clinically indicated.

These language barriers affect patients on many levels – in their ability to understand instructions for medication administration, preparation for procedures, and return precautions – which may ultimately lead to poorer responses to therapy or delays in care. LEP alone is broadly associated with fewer referrals for outpatient follow-up, adverse health outcomes and complications, and longer hospital stays.⁹ These disparities can be mitigated by investing in high-quality interpreter services, providing instructions and forms in multiple languages, and engaging the patient’s family and social supports according to their preferences.

People experiencing poverty (urban and rural) face challenges across multiple domains including access to healthcare, health insurance, stable housing and employment, and more. Many patients seek care at federally qualified health centers, which may face greater difficulties coordinating care with external gastroenterologists.¹⁰

 

Insurance barriers limit access to essential medications, tests, and procedures, and create delays in establishing care with specialists. Significant psychological stress and higher rates of comorbid anxiety and depression contribute to increased IBS severity.¹¹ Financial limitations may limit dietary choices, which can further exacerbate DGBI symptoms. Long work hours with limited flexibility may prohibit them from presenting for regular follow-ups and establishing advanced DGBI care such as with a dietitian or psychologist.

Patients with disabilities face many of the health inequities previously discussed, as well as additional challenges with physical accessibility, transportation, exclusion from education and employment, discrimination, and stigma. Higher prevalence of comorbid mental illness and higher rates of intimate partner violence and interpersonal violence all contribute to DGBI severity and challenges with access to care.^12,13 Patients with disabilities may struggle to arrive at appointments, maneuver through the building or exam room, and ultimately follow recommended care plans.

 

How to approach DGBIs in historically marginalized and minoritized communities

Returning to the patients from the introduction, how would you counsel each of them?

Patient 1: We can discuss with the patient how nortriptyline and other typical antidepressants can and often are used for indications other than depression. These medications modify centrally-mediated pain signaling and many patients with functional dyspepsia experience a significant benefit. It is critical to build on the rapport that was established at the community health outreach event and to explore the patient’s concerns thoroughly.

Patient 2: We would begin by inquiring about her underlying fears associated with her symptoms and seek to understand her goals for repeat intervention. We can review the risks of endoscopy and shift the focus to improving her symptoms. If we can improve her bowel habits or her pain, her desire for further interventions may lessen. 

Patient 3: It will be important to work within the realistic time and monetary constraints in this patient’s life. We can validate him and the challenges he is facing, provide positive reinforcement for the progress he has made so far, and avoid disparaging him for the aspects of the treatment plan he has been unable to follow through with. As he reported a benefit from amitriptyline, we can consider increasing his dose as a feasible next step. 

Patient 4: We can encourage the patient to discuss with his primary care physician how they may be able to coordinate an inpatient admission for colonoscopy preparation. Given his co-morbidities, this avenue will provide him dedicated support to help him adequately prep to ensure a higher quality examination and limit the need for repeat procedures.

DGBI care in historically marginalized and minoritized communities: A call to action

Understanding cultural differences and existing disparities in care is essential to improving care for patients from historically minoritized communities with DGBIs. Motivational interviewing and shared decision-making, with acknowledgment of social and cultural differences, allow us to work together with patients and their support systems to set and achieve feasible goals.¹⁴

 

To address known health disparities, offices can take steps to ensure the accessibility of language, forms, physical space, providers, and care teams. Providing culturally sensitive care and lowering barriers to care are the first steps to effecting meaningful change for patients with DGBIs from historically minoritized communities.

Dr. Yu is based at Division of Gastroenterology and Hepatology, Boston Medical Center and Boston University, both in Boston, Massachusetts. Dr. Dimino and Dr. Vélez are based at the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, both in Boston, Massachusetts. Dr. Yu, Dr. Dimino, and Dr. Vélez do not have any conflicts of interest for this article.

Additional Online Resources

Form Accessibility 

• Intake Form Guidance for Providers
• Making Your Clinic Welcoming to LGBTQ Patients
• Transgender data collection in the electronic health record: Current concepts and issues

Language Accessibility 

• Overcoming the challenges of providing care to limited English proficient patients

Physical Accessibility 

• Access to Medical Care for Individuals with Mobility Disabilities
• Making your medical office accessible

References

1. Zavala VA, et al. Cancer health disparities in racial/ethnic minorities in the United States. Br J Cancer. 2021 Jan. doi: 10.1038/s41416-020-01038-6.

2. Kardashian A, et al. Health disparities in chronic liver disease. Hepatology. 2023 Apr. doi: 10.1002/hep.32743.

3. Nephew LD, Serper M. Racial, Gender, and Socioeconomic Disparities in Liver Transplantation. Liver Transpl. 2021 Jun. doi: 10.1002/lt.25996.

4. Anyane-Yeboa A, et al. The Impact of the Social Determinants of Health on Disparities in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2022 Nov. doi: 10.1016/j.cgh.2022.03.011.

5. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb. doi: 10.1053/j.gastro.2016.02.032.

6. Silvernale C, et al. Racial disparity in healthcare utilization among patients with Irritable Bowel Syndrome: results from a multicenter cohort. Neurogastroenterol Motil. 2021 May. doi: 10.1111/nmo.14039.

7. Hearn M, et al. Stigma and irritable bowel syndrome: a taboo subject? Lancet Gastroenterol Hepatol. 2020 Jun. doi: 10.1016/S2468-1253(19)30348-6.

8. Yan XJ, et al. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb. doi: 10.1111/nmo.13956.

9. Twersky SE, et al. The Impact of Limited English Proficiency on Healthcare Access and Outcomes in the U.S.: A Scoping Review. Healthcare (Basel). 2024 Jan. doi: 10.3390/healthcare12030364.

10. Bayly JE, et al. Limited English proficiency and reported receipt of colorectal cancer screening among adults 45-75 in 2019 and 2021. Prev Med Rep. 2024 Feb. doi: 10.1016/j.pmedr.2024.102638.

11. Cheng K, et al. Epidemiology of Irritable Bowel Syndrome in a Large Academic Safety-Net Hospital. J Clin Med. 2024 Feb. doi: 10.3390/jcm13051314.

12. Breiding MJ, Armour BS. The association between disability and intimate partner violence in the United States. Ann Epidemiol. 2015 Jun. doi: 10.1016/j.annepidem.2015.03.017.

13. Mitra M, et al. Prevalence and characteristics of sexual violence against men with disabilities. Am J Prev Med. 2016 Mar. doi: 10.1016/j.amepre.2015.07.030.

14. Bahafzallah L, et al. Motivational Interviewing in Ethnic Populations. J Immigr Minor Health. 2020 Aug. doi: 10.1007/s10903-019-00940-3.

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com . 

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com . 

Walnut consumption modified the fecal microbiota and metabolome, improved insulin response, and reduced gut permeability in adults with obesity, a small study showed.

“Less than 10% of adults are meeting their fiber needs each day, and walnuts are a source of dietary fiber, which helps nourish the gut microbiota,” study coauthor Hannah Holscher, PhD, RD, associate professor of nutrition at the University of Illinois at Urbana-Champaign, told GI & Hepatology News.

Holscher and her colleagues previously conducted a study on the effects of walnut consumption on the human intestinal microbiota “and found interesting results,” she said. Among 18 healthy men and women with a mean age of 53 years, “walnuts enriched intestinal microorganisms, including Roseburia that provide important gut-health promoting attributes, like short-chain fatty acid production. We also saw lower proinflammatory secondary bile acid concentrations in individuals that ate walnuts.”

The current study, presented at NUTRITION 2025 in Orlando, Florida, found similar benefits among 30 adults with obesity but without diabetes or gastrointestinal disease.

 

Walnut Halves, Walnut Oil, Corn Oil — Compared

The researchers aimed to determine the impact of walnut consumption on the gut microbiome, serum and fecal bile acid profiles, systemic inflammation, and oral glucose tolerance to a mixed-meal challenge.

Participants were enrolled in a randomized, controlled, crossover, complete feeding trial with three 3-week conditions, each identical except for walnut halves (WH), walnut oil (WO), or corn oil (CO) in the diet. A 3-week washout separated each condition.

“This was a fully controlled dietary feeding intervention,” Holscher said. “We provided their breakfast, lunch, snacks and dinners — all of their foods and beverages during the three dietary intervention periods that lasted for 3 weeks each. Their base diet consisted of typical American foods that you would find in a grocery store in central Illinois.”

Fecal samples were collected on days 18-20. On day 20, participants underwent a 6-hour mixed-meal tolerance test (75 g glucose + treatment) with a fasting blood draw followed by blood sampling every 30 minutes.

The fecal microbiome and microbiota were assessed using metagenomic and amplicon sequencing, respectively. Fecal microbial metabolites were quantified using gas chromatography-mass spectrometry.

Blood glucose, insulin, and inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha, C-reactive protein, and lipopolysaccharide-binding protein) were quantified. Fecal and circulating bile acids were measured via liquid chromatography tandem mass spectrometry.

Gut permeability was assessed by quantifying 24-hour urinary excretion of orally ingested sucralose and erythritol on day 21.

Linear mixed-effects models and repeated measures ANOVA were used for the statistical analysis.

The team found that Roseburia spp were greatest following WH (3.9%) vs WO (1.6) and CO (1.9); Lachnospiraceae UCG-001 and UCG-004 were also greatest with WH vs WO and CO.

WH fecal isobutyrate concentrations (5.41 µmol/g) were lower than WO (7.17 µmol/g) and CO (7.77). Similarly, fecal isovalerate concentrations were lowest with WH (7.84 µmol/g) vs WO (10.3µmol/g) and CO (11.6 µmol/g).

In contrast, indoles were highest in WH (36.8 µmol/g) vs WO (6.78 µmol/g) and CO (8.67µmol/g).

No differences in glucose concentrations were seen among groups. The 2-hour area under the curve (AUC) for insulin was lower with WH (469 µIU/mL/min) and WO (494) vs CO (604 µIU/mL/min).

The 4-hour AUC for glycolithocholic acid was lower with WH vs WO and CO. Furthermore, sucralose recovery was lowest following WH (10.5) vs WO (14.3) and CO (14.6).

“Our current efforts are focused on understanding connections between plasma bile acids and glycemic control (ie, blood glucose and insulin concentrations),” Holscher said. “We are also interested in studying individualized or personalized responses, since people had different magnitudes of responses.”

In addition, she said, “as the gut microbiome is one of the factors that can underpin the physiological response to the diet, we are interested in determining if there are microbial signatures that are predictive of glycemic control.”

Because the research is still in the early stages, at this point, Holscher simply encourages people to eat a variety of fruits, vegetables, whole grains, legumes and nuts to meet their daily fiber recommendations and support their gut microbiome.

This study was funded by a USDA NIFA grant. No competing interests were reported.

A version of this article appeared on Medscape.com .