Psychoneurogastroenterology: The abdominal brain, the microbiome, and psychiatry

This nervous system is located inside the wall of the GI tract, extending from the esophagus to the rectum. Technically, it is known as the enteric nervous system, or ENS, but it has been given other labels, too: “second brain,”² “abdominal brain,” “other brain,” and “back-up brain.” Its neurologic disorders include abdomi­nal epilepsy, abdominal migraine, and autism with intestinal symptoms, such as chronic enterocolitis.³

Impressive brain-like features
The ENS includes 100 million neu­rons (same as the spinal cord) with glia-like support cells. It contains >30 neurotransmitters, including several closely linked to psychopathology (serotonin, dopamine, γ-aminobutyric acid, and acetylcholine). The ENS is not part of the autonomic nervous system. It communicates with the brain via the vagus nerve.

A vast system of gut bacteria
The ENS maintains close links with, and is influenced by, the microbiome, an extensive universe of commensal (that is, symbiotic) bacteria in the gut that play a vital role in immune health, brain function, and signaling systems within the CNS. The role of the micro­biome in neuropsychiatric disorders has become a sizzling area of research.

The numbers of the microbiome are astonishing, including approximately 1,000 species of bacteria; 100 trillion total bacterial organisms (outnum­bering cells of the body by 100-fold); 4 million bacterial genes (compared with 26,000 genes in the host human genome); and a density as high as 1 tril­lion bacteria in a cubic milliliter—higher than any known microbial system.⁴

Significant GI−brain connections
It is of great relevance to psychiatry that 90% of the body’s serotonin and 50% of dopamine are found in the GI brain. Selective serotonin reuptake inhibitors often are associated with GI symptoms, such as nausea and diarrhea; antipsychotics, which are dopamine antagonists, are known for antiemetic effects. Clozapine’s potent anticholiner­gic effects can cause serious ileus.

Things get more interesting when one considers the association of GI dis­orders and psychiatric symptoms:

Irritable bowel syndrome is associated with panic disorder, generalized anxiety disorder, social phobia, dysthymia, and major depression.

Inflammatory bowel disease (IBD)— such as Crohn’s disease and ulcerative colitis (prevalence ranging from 6% in Canada to 14% in the United States to 46% in Mexico⁵)—is commonly associ­ated with mood and anxiety disorders and personality changes. The psychi­atric manifestations of IBD are so com­mon that the authors of a recent article in World Journal of Gastroenterology urged gastroenterologists to collaborate with psychiatrists when managing IBD.⁶

Celiac disease has been repeatedly associated with several neuropsychiat­ric disorders, including ataxia, epilepsy, peripheral neuropathy, headache, anxi­ety, attention-deficit/hyperactivity dis­order, autism spectrum disorder, and schizophrenia.

New, exciting challenges for medical science
There potentially are important impli­cations for possible exploitation of the ENS and the microbiome in the diag­nosis and treatment of neuropsychiatric disorders. For example, consider these speculative challenges:
   • Can intestinal biopsy reveal neu­rotransmitter pathology in schizophrenia?
   • Can early dopamine deficiency predict Parkinson’s disease, enabling early intervention?
   • Can β-amyloid deposits, the degenerative neurologic stigmata of Alzheimer’s disease, be detected in abdominal neurons years before onset of symptoms to allow early intervention?
   • Can the ENS become a therapeutic pathway by targeting the various neu­rotransmitters found there or by engag­ing the enormous human microbiome to manipulate its beneficial properties?
   • Can foods or probiotic supple­ments be prescribed as microbiomal adjuncts to improve the mood and anxi­ety spectrum?

One recommendation I came across is that ingesting 10 to 100 million ben­eficial bacteria, such as Lactobacillus plan­tarum and Bifidobacterium infantis, might be helpful. Such prescriptions obviously are speculative but also are reasonably testable hypotheses of ways to exploit the “other brain” and the microbiome.

We must summon the guts to seize this opportunity
An independent second brain and a remarkable microbiome appear to be significant evolutionary adaptations and advantages for humans. For too long, neuropsychiatric researchers have ignored the ENS and the micro­biome; now, they must focus on how to exploit these entities to yield inno­vative diagnostic and therapeutic advances. Integrating the ENS and the microbiome and enmeshing them into neuropsychiatric research and clinical applications hold great promise.

The field of psychoneurogastroen­terology is in its infancy, but its growth and relevance will be momentous for neuropsychiatry. A major intellectual peristalsis is underway.

This nervous system is located inside the wall of the GI tract, extending from the esophagus to the rectum. Technically, it is known as the enteric nervous system, or ENS, but it has been given other labels, too: “second brain,”² “abdominal brain,” “other brain,” and “back-up brain.” Its neurologic disorders include abdomi­nal epilepsy, abdominal migraine, and autism with intestinal symptoms, such as chronic enterocolitis.³

Impressive brain-like features
The ENS includes 100 million neu­rons (same as the spinal cord) with glia-like support cells. It contains >30 neurotransmitters, including several closely linked to psychopathology (serotonin, dopamine, γ-aminobutyric acid, and acetylcholine). The ENS is not part of the autonomic nervous system. It communicates with the brain via the vagus nerve.

A vast system of gut bacteria
The ENS maintains close links with, and is influenced by, the microbiome, an extensive universe of commensal (that is, symbiotic) bacteria in the gut that play a vital role in immune health, brain function, and signaling systems within the CNS. The role of the micro­biome in neuropsychiatric disorders has become a sizzling area of research.

The numbers of the microbiome are astonishing, including approximately 1,000 species of bacteria; 100 trillion total bacterial organisms (outnum­bering cells of the body by 100-fold); 4 million bacterial genes (compared with 26,000 genes in the host human genome); and a density as high as 1 tril­lion bacteria in a cubic milliliter—higher than any known microbial system.⁴

Significant GI−brain connections
It is of great relevance to psychiatry that 90% of the body’s serotonin and 50% of dopamine are found in the GI brain. Selective serotonin reuptake inhibitors often are associated with GI symptoms, such as nausea and diarrhea; antipsychotics, which are dopamine antagonists, are known for antiemetic effects. Clozapine’s potent anticholiner­gic effects can cause serious ileus.

Things get more interesting when one considers the association of GI dis­orders and psychiatric symptoms:

Irritable bowel syndrome is associated with panic disorder, generalized anxiety disorder, social phobia, dysthymia, and major depression.

Inflammatory bowel disease (IBD)— such as Crohn’s disease and ulcerative colitis (prevalence ranging from 6% in Canada to 14% in the United States to 46% in Mexico⁵)—is commonly associ­ated with mood and anxiety disorders and personality changes. The psychi­atric manifestations of IBD are so com­mon that the authors of a recent article in World Journal of Gastroenterology urged gastroenterologists to collaborate with psychiatrists when managing IBD.⁶

Celiac disease has been repeatedly associated with several neuropsychiat­ric disorders, including ataxia, epilepsy, peripheral neuropathy, headache, anxi­ety, attention-deficit/hyperactivity dis­order, autism spectrum disorder, and schizophrenia.

New, exciting challenges for medical science
There potentially are important impli­cations for possible exploitation of the ENS and the microbiome in the diag­nosis and treatment of neuropsychiatric disorders. For example, consider these speculative challenges:
   • Can intestinal biopsy reveal neu­rotransmitter pathology in schizophrenia?
   • Can early dopamine deficiency predict Parkinson’s disease, enabling early intervention?
   • Can β-amyloid deposits, the degenerative neurologic stigmata of Alzheimer’s disease, be detected in abdominal neurons years before onset of symptoms to allow early intervention?
   • Can the ENS become a therapeutic pathway by targeting the various neu­rotransmitters found there or by engag­ing the enormous human microbiome to manipulate its beneficial properties?
   • Can foods or probiotic supple­ments be prescribed as microbiomal adjuncts to improve the mood and anxi­ety spectrum?

One recommendation I came across is that ingesting 10 to 100 million ben­eficial bacteria, such as Lactobacillus plan­tarum and Bifidobacterium infantis, might be helpful. Such prescriptions obviously are speculative but also are reasonably testable hypotheses of ways to exploit the “other brain” and the microbiome.

We must summon the guts to seize this opportunity
An independent second brain and a remarkable microbiome appear to be significant evolutionary adaptations and advantages for humans. For too long, neuropsychiatric researchers have ignored the ENS and the micro­biome; now, they must focus on how to exploit these entities to yield inno­vative diagnostic and therapeutic advances. Integrating the ENS and the microbiome and enmeshing them into neuropsychiatric research and clinical applications hold great promise.

The field of psychoneurogastroen­terology is in its infancy, but its growth and relevance will be momentous for neuropsychiatry. A major intellectual peristalsis is underway.

This nervous system is located inside the wall of the GI tract, extending from the esophagus to the rectum. Technically, it is known as the enteric nervous system, or ENS, but it has been given other labels, too: “second brain,”² “abdominal brain,” “other brain,” and “back-up brain.” Its neurologic disorders include abdomi­nal epilepsy, abdominal migraine, and autism with intestinal symptoms, such as chronic enterocolitis.³

Impressive brain-like features
The ENS includes 100 million neu­rons (same as the spinal cord) with glia-like support cells. It contains >30 neurotransmitters, including several closely linked to psychopathology (serotonin, dopamine, γ-aminobutyric acid, and acetylcholine). The ENS is not part of the autonomic nervous system. It communicates with the brain via the vagus nerve.

A vast system of gut bacteria
The ENS maintains close links with, and is influenced by, the microbiome, an extensive universe of commensal (that is, symbiotic) bacteria in the gut that play a vital role in immune health, brain function, and signaling systems within the CNS. The role of the micro­biome in neuropsychiatric disorders has become a sizzling area of research.

The numbers of the microbiome are astonishing, including approximately 1,000 species of bacteria; 100 trillion total bacterial organisms (outnum­bering cells of the body by 100-fold); 4 million bacterial genes (compared with 26,000 genes in the host human genome); and a density as high as 1 tril­lion bacteria in a cubic milliliter—higher than any known microbial system.⁴

Significant GI−brain connections
It is of great relevance to psychiatry that 90% of the body’s serotonin and 50% of dopamine are found in the GI brain. Selective serotonin reuptake inhibitors often are associated with GI symptoms, such as nausea and diarrhea; antipsychotics, which are dopamine antagonists, are known for antiemetic effects. Clozapine’s potent anticholiner­gic effects can cause serious ileus.

Things get more interesting when one considers the association of GI dis­orders and psychiatric symptoms:

Irritable bowel syndrome is associated with panic disorder, generalized anxiety disorder, social phobia, dysthymia, and major depression.

Inflammatory bowel disease (IBD)— such as Crohn’s disease and ulcerative colitis (prevalence ranging from 6% in Canada to 14% in the United States to 46% in Mexico⁵)—is commonly associ­ated with mood and anxiety disorders and personality changes. The psychi­atric manifestations of IBD are so com­mon that the authors of a recent article in World Journal of Gastroenterology urged gastroenterologists to collaborate with psychiatrists when managing IBD.⁶

Celiac disease has been repeatedly associated with several neuropsychiat­ric disorders, including ataxia, epilepsy, peripheral neuropathy, headache, anxi­ety, attention-deficit/hyperactivity dis­order, autism spectrum disorder, and schizophrenia.

New, exciting challenges for medical science
There potentially are important impli­cations for possible exploitation of the ENS and the microbiome in the diag­nosis and treatment of neuropsychiatric disorders. For example, consider these speculative challenges:
   • Can intestinal biopsy reveal neu­rotransmitter pathology in schizophrenia?
   • Can early dopamine deficiency predict Parkinson’s disease, enabling early intervention?
   • Can β-amyloid deposits, the degenerative neurologic stigmata of Alzheimer’s disease, be detected in abdominal neurons years before onset of symptoms to allow early intervention?
   • Can the ENS become a therapeutic pathway by targeting the various neu­rotransmitters found there or by engag­ing the enormous human microbiome to manipulate its beneficial properties?
   • Can foods or probiotic supple­ments be prescribed as microbiomal adjuncts to improve the mood and anxi­ety spectrum?

One recommendation I came across is that ingesting 10 to 100 million ben­eficial bacteria, such as Lactobacillus plan­tarum and Bifidobacterium infantis, might be helpful. Such prescriptions obviously are speculative but also are reasonably testable hypotheses of ways to exploit the “other brain” and the microbiome.

We must summon the guts to seize this opportunity
An independent second brain and a remarkable microbiome appear to be significant evolutionary adaptations and advantages for humans. For too long, neuropsychiatric researchers have ignored the ENS and the micro­biome; now, they must focus on how to exploit these entities to yield inno­vative diagnostic and therapeutic advances. Integrating the ENS and the microbiome and enmeshing them into neuropsychiatric research and clinical applications hold great promise.

The field of psychoneurogastroen­terology is in its infancy, but its growth and relevance will be momentous for neuropsychiatry. A major intellectual peristalsis is underway.