User login
How Exactly Does One Map the Human Gut?
There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.
“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.
No small question: How, exactly, does one go about mapping the human gut?
Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.
How It Began
Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.
Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.
In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.
“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”
Not a Bad ‘Lockdown Project’
During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).
“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.
She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.
In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.
How to Build a Two-Dimensional (2D) Map of the Gut
Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.
“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.
Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.
“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.
For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”
In Brutal Detail
One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.
For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.
“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.
Before ‘Eureka’ Comes a Few ‘Aha’ Moments
There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.
“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.
Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.
They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.
“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.
In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.
A Gut Cell Atlas for the People (Well, Scientific People)
“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.
Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.
At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.
He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.
“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.
He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.”
Next Step: Visualize It in a Three-Dimensional (3D) Space
The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.
“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”
A version of this article appeared on Medscape.com.
There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.
“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.
No small question: How, exactly, does one go about mapping the human gut?
Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.
How It Began
Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.
Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.
In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.
“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”
Not a Bad ‘Lockdown Project’
During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).
“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.
She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.
In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.
How to Build a Two-Dimensional (2D) Map of the Gut
Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.
“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.
Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.
“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.
For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”
In Brutal Detail
One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.
For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.
“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.
Before ‘Eureka’ Comes a Few ‘Aha’ Moments
There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.
“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.
Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.
They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.
“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.
In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.
A Gut Cell Atlas for the People (Well, Scientific People)
“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.
Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.
At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.
He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.
“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.
He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.”
Next Step: Visualize It in a Three-Dimensional (3D) Space
The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.
“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”
A version of this article appeared on Medscape.com.
There was a recent flurry of excitement when UK researchers from the Wellcome Sanger Institute, a nonprofit genomics and genetics research organization in Cambridge, England, announced their creation of the most detailed cell map of the human gastrointestinal (GI) tract up to this point. Using spatial and single-cell data from 1.6 million cells (from 271 donors), the scientists’ work, published in Nature, yields valuable information about the gut’s health and disease states.
“We now have a nice idea of what cell types we can find in the gut,” said co-author Rasa Elmentaite, PhD, co-founder and head of Genomics and Data Science at Ensocell.
No small question: How, exactly, does one go about mapping the human gut?
Most of all, Elmentaite said, it has taken the scientists involved down paths they never anticipated.
How It Began
Over the past 5-7 years, there have been many individual publications across institutes where research labs have created snippets of what the cells in the gut look like, said Elmentaite, referring to the GI tract, which in this case encompasses the mouth, throat, esophagus, stomach, small intestine, large intestine, rectum, and anus.
Labs studying gut cells often focus on one specific region, for example, the small intestine or the large intestine, if they’re working on Crohn’s disease research. “It makes sense. The GI tract is really regionalized,” she said.
In 2019 and 2021, Elmentaite and her colleagues published papers that mapped some cells in the human gut, and their work garnered attention from other scientists around the world. That’s how they decided to take on the challenge of creating a more comprehensive map of the cells in both the healthy gut and in GI tracts where disease is present.
“We realized there are so many other labs interested in understanding the intestinal tract holistically,” she said. “We thought it would be really interesting to look at the cells in the context of the whole GI system.”
Not a Bad ‘Lockdown Project’
During the pandemic, while the rest of society was playing with sourdough starter, Elmentaite’s lab decided to pool their datasets with data from other labs to see what happened. They had more than 20 datasets at the time and wanted to generate more to fill gaps where there was less information available (eg, data on the cells in the stomach).
“It required getting samples from surgeons, going into the lab and processing those samples into single cells, and then processing that data bioinformatically,” said Elmentaite.
She explained that generating more datasets was not a job for one person and “required convincing a lot of scientists that it was worthwhile,” including a cancer biologist and a mucosal immunologist. They also brought in more technical bioinformatics expertise and recruited an IT team — several people who only worked on processing data and clearing it, “so it was aligned very specifically, and processed very uniformly, across the study,” Elmentaite said.
In the end, with researchers coming together on many Zoom calls from Australia, Germany, Norway, Spain, and numerous locations across the United Kingdom, they were able to integrate 25 single-cell RNA sequencing datasets that encompassed the entire healthy GI tract in development and in adults, leading to a healthy gut reference atlas that includes about 1.1 million cells and 136 cell subgroups.
How to Build a Two-Dimensional (2D) Map of the Gut
Here’s where the weeds get taller: Raw sequencing reads — bits of different RNA that the researchers sequenced from individual biological samples — needed to be mapped back to genes so that the researchers could understand what kinds of genes were expressed in the samples.
“There is a lot of curation there that needs to happen because the versions of transcriptome [a complete set of RNA molecules in a single cell or tissue], and what the genome looks like, is evolving constantly. So we have to map it back to the same transcriptomic reference,” Elmentaite said.
Once they knew all the different genes active in a cell, the researchers were able, using bioinformatics, to pull all of the datasets together and visualize them in a 2D space — essentially, a representation of a map.
“The cells that are transcriptionally more similar to each other, they will cluster together. And the ones that are more distinct transcriptionally will be farther away from each other,” Elmentaite said.
For decades, GI tract researchers had individually studied which types of genes are activated in an epithelial cell vs a T cell vs a B cell, she said, and “then suddenly you’re seeing it on your screen all at once. It’s amazing to see.”
In Brutal Detail
One of the biggest challenges in interpreting the data involved many people who made sure that there were no technical differences between the samples, Elmentaite said.
For example, samples processed in different labs may have sequencing differences between them. Or the kind of enzymes used to process the tissue might have been different from lab to lab. Sometimes they’d even record down to the detail what time of the day a sample was collected, if that information was available.
“Computationally, we considered all of these variables and tried to regress as much of that as possible. And then, if we saw clusters that resembled gene expression that we know is consistent with some of the cell types, then we knew that we’d regressed all the batch effects,” said Elmentaite.
Before ‘Eureka’ Comes a Few ‘Aha’ Moments
There were many “aha moments,” but also some puzzling ones, she said. One of the biggest surprises was seeing that the identity of a cell believed to be set from development can actually change if a person has a lot of irritation and inflammation, as occurs in inflammatory bowel disease. Epithelial cell metaplasia was one of the surprises.
“Metaplasia describes an activation or differentiation of one differentiated cell type into another differentiated cell type. And we knew that that exists in some of the upper GI diseases, but we didn’t realize that the same sort of mechanism exists in the small intestine,” Elmentaite said.
Epithelial cells are among the most abundant cells in the body. The researchers knew from established research that these cells act a bit like first responders and provide healing to the gut. “We could see that they were producing a lot of mucous that helps to potentially flush down the microbes that are triggering inflammation. But the ‘aha moment’ for us was that actually there’s a dual function in these cells,” she said.
They could see in the transcriptional profile a significant production of chemokines (a family of proteins that play a role in the body’s immune responses) and major histocompatibility complex class II molecules (cell surface proteins involved in the body’s immune response), and the epithelial cells seemed to attract neutrophils and monocytes and to interact with certain T cells — adding to the cycle of chronic inflammation.
“I think for a lot of us, this was a surprise because we think of epithelial cells as more like a barrier, just a passive player in, for example, inflammatory bowel disease,” said Elmentaite.
In addition to reporting their findings on epithelial cell metaplasia, the researchers processed 12 GI disease datasets, including celiac disease, Crohn’s disease, GI-related cancers, and ulcerative colitis.
A Gut Cell Atlas for the People (Well, Scientific People)
“The Gut Cell Atlas is usable for everyone, and everyone has a chance to contribute,” said Elmentaite. But 1.6 million cells is only a start and more data are needed, she said, and efforts are being spearheaded at the broader Human Cell Atlas project to collect it. There are also efforts to get all researchers using the same cell annotation, research-wide standards that will make the atlas truly usable for everyone.
Keith Summa, MD, PhD, assistant professor of medicine in the Division of Gastroenterology and Hepatology at Feinberg School of Medicine, Northwestern University, Chicago, focuses much of his work on inflammatory bowel disease as well as disorders of the gut-brain interaction. He conducts basic and translational research using experimental models of intestinal inflammation.
At Northwestern University, they have a tissue biorepository. It includes colon and intestine tissue samples from healthy individuals as well as individuals with different disease states. “One potential area where I could see this being a useful tool for us is that we could utilize the Gut Cell Atlas in the analysis of our tissue samples to see if we find commonalities between what’s described in the atlas and then what we’re observing,” said Summa, who was not involved in the UK-based project.
He said Northwestern University’s biorepository has details about what medications people were on and the extent and severity of their disease.
“We may be able to utilize the Gut Cell Atlas to help us look at specific factors in terms of how people are responding to different treatments, how different cell types are affected by different treatments, or how they are active or not active in different severities of disease. It may help us provide more precision to our understanding of these different conditions,” said Summa.
He also noted how GI specialists use “Crohn’s disease” as a single diagnosis, “but that encompasses a pretty wide spectrum of phenotypes and behaviors,” he said. “I think looking at such a cell-specific level may help to better identify some of the different pathways that are active and the different phenotypes or behaviors of this disease.”
Next Step: Visualize It in a Three-Dimensional (3D) Space
The next stage for Elmentaite and her colleagues is to evolve the 2D map into a 3D map so they can visualize which cells are where and how they are organized in space.
“The next step, which I think is super exciting, is understanding how these cells depend on each other,” she said. “Really functionally understanding if some of them are essential and others are not. And doing AI modeling to understand what we can learn from this vast amount of data that we’re generating. And of course, that includes how we use this knowledge to create precision therapies.”
A version of this article appeared on Medscape.com.
Scientists Create First Map of a Human Ovary: What to Know
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
For years, scientists have sought to create a human artificial ovary, restoring fertility in patients without other options. The first cellular map of a human ovary, recently developed at the University of Michigan, Ann Arbor, represents a big leap forward in that quest.
“You cannot build something if you don’t have the blueprint,” said biomedical engineer Ariella Shikanov, PhD, associate professor at University of Michigan, who helped create what she and colleagues call an atlas of the ovary. “By creating a map or an atlas, we can now follow what nature created and engineer the building blocks of an ovary — and build a nature-like structure.”
So far, the concept of an artificial ovary has been successful only in mice, with the development of a 3D-printed prosthetic ovary that enabled sterilized mice to have pups. Researchers hope that artificial human ovary technology could someday help women left infertile after cancer treatment, as well as patients who don›t respond to fertility treatments and those with premature ovarian failure.
But Dr. Shikanov believes this research will go even further, providing a valuable resource to scientists studying diseases and other conditions related to the ovary.
“Whenever people think about the ovary, if they think about it at all, they usually think about fertility,” said Dr. Shikanov. The ovary is so much more.
Besides producing and carrying a woman’s unfertilized eggs during her lifetime, the ovary is also responsible for endocrine function — the production of estrogen and progesterone, which in addition to supporting reproductive health, help maintain a woman’s cardiovascular, bone, and mental health.
“We don’t really understand everything that is happening in the ovary yet,” Dr. Shikanov said. “But we know it is an important organ.”
Mapping the Ovary
Because people don’t typically donate their ovaries, there are not many available for research, especially from younger reproductive age women, said Dr. Shikanov. So, the scientists set out to build a resource. They described their work in Science Advances.
To create their atlas, the researchers studied two premenopausal donor ovaries, profiling 18,000 genes in 257 regions. From three additional donor ovaries, they also generated single-cell RNA sequencing data for 21,198 cells.
“We identified four major cell types and four immune cell subtypes in the ovary,” said Dr. Shikanov. Taking samples from different areas of the ovary revealed distinct gene activities for oocytes, theca cells, and granulosa cells — expanding scientists’ understanding of the molecular programs driving ovarian follicle development.
What’s unique about their work is the focus on both single cell and spatial analysis, said study coauthor Jun Z. Li, PhD, associate chair of the University of Michigan’s department of computational medicine and bioinformatics. Specifically, they used a relatively new method called spatial transcriptomics, which allows them to see which genes are being activated and where.
“We are constructing the spatial arrangement of the cells in the ovary,” said Dr. Li. “This spatial analysis is like saying, ‘Let me look at where you are and who your neighbor is.’ ”
Their findings are built on other genetic and cellular research in the field, Dr. Li noted. Biomedical engineers in other areas of medicine are applying similar technologies to other organs including the heart, the breast, and bone — part of a larger project called the Human Cell Atlas.
Advancing Women’s Health Research
Historically, women’s health research has been underfunded and underrepresented, but the authors believe their atlas of the ovary is a significant step forward.
“There are a lot of biological questions that we don’t know the answers to about the ovary,” said Dr. Shikanov.
One of the biggest mysteries is why so many eggs never become fertilizable. Each human female is born with about one to two million ovarian follicles. Each follicle carries one immature egg. Around puberty, two thirds of these follicles die off. And most that are left never develop into fertilizable eggs.
“The majority of these follicles either just grow and secrete hormones or undergo atresia,” Dr. Shikanov said. “One question that we wanted to understand is, what determines an egg that can grow, ovulate, and become a fertilizable egg and potentially develop into a new human being from one that does not?”
Another big question researchers have is, what’s happening with other types of cells in the ovary — the supporting cells that produce endocrine hormones? Where are they located and what proteins and RNA are they making? Their research begins to unravel some of these questions and lays a foundation for future studies.
“We wanted to analyze the transcriptional signatures from specific regions and then do bioinformatical analysis and really combine structure, function, and transcriptional signatures,” Dr. Shikanov said.
Knowing the transcriptional signatures can help researchers understand disease mechanisms and then go on to develop treatments for these diseases.
Winifred Mak, MD, PhD, a reproductive endocrinologist and infertility specialist at Dell Medical School, University of Texas, Austin, studies cancer fertility preservation. “For me, it is interesting to see that there are so many different clusters of cells in the ovary that have been identified by this study that we were not necessarily aware of before,” said Dr. Mak, who is not involved in the new research. “Also, the identification of new genes not previously studied in the human ovary.”
What’s Next
Dozens of scientists who study reproductive health are already reaching out to the researchers about their work, Dr. Shikanov said.
“We get contacted almost every day from researchers all around the world asking for data sets or asking for details from this paper,” she said, “from people who study ovarian cancer, for example.”
Dr. Mak said having a map of a normal ovary could also help researchers who study premature ovarian insufficiency — why the ovary sometimes goes into premature menopause — and polycystic ovarian syndrome.
Another big area of research interest is ovarian aging. “Women live so much longer now, but we still reach menopause at the age of 50,” Dr. Shikanov said. “So, there are efforts going toward understanding ovarian aging and maybe preventing it to extend ovarian longevity.”
Dr. Mak said it will enable scientists to “look at different age women and see what genes change across the reproductive lifespan.”
The atlas may also eventually lead to treatments that help restore fertility in individuals who had and were treated for cancer as children, people who undergo sex transitions, and those whose reproductive organs have been impacted by trauma in conflict settings or accidents, Dr. Li said.
The applications are numerous and exciting, Dr. Shikanov said. “Our atlas is like a benchmark. Now researchers can collect ovaries from individuals with these diseases and conditions and try to compare what’s different.”
A version of this article appeared on Medscape.com.
Poop Doesn’t Lie: What Fecal ‘Forensics’ Tells Us About Diet
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
A lightbulb moment hit as Lawrence David was chatting one day with an ecologist who studies the microbiomes and diets of large herbivores in the African savanna. David was envious. He’d been studying the human microbiome, and this ecologist had tons of animal statistics that were way more specific than what David had obtained from people.
“How on earth do you get all these dietary data?” David recalled asking. “Obviously, he didn’t ask the animals what they ate.”
All those specific statistics came from DNA sequencing of animal scat scooped up from the savanna.
Indeed.
Depending on when you read this, you may have the DNA of more than a dozen plant species, plus another three or four animal species, gurgling through your gut. That’s the straight poop taken straight from, well, poop.
Diet, DNA, and Feces
Everything we eat (except vitamins, minerals, and salt) came from something that was living, and all living things have genomes.
“A decent fraction of that DNA” goes undigested and is then excreted, said David, a PhD and associate professor of molecular genetics and microbiology at Duke University, Durham, North Carolina.
“We are using DNA sequencing to reconstruct what people eat,” David said. “We try to see if there are patterns in what people eat and how we can measure them by DNA, or kind of genetic forensics.” Then they connect that data to health outcomes like obesity.
A typical person’s excrement probably contains the DNA of 10-20 plant species and three or four types of animal DNA. “And that’s the average person. Some people may have more like 40 types at any given time,” David said.
Studying DNA in human feces has potential applications in research and in clinical settings. For instance, it could help design personalized nutrition strategies for patients, something that’s already being tested. He hopes that DNA information will help “connect patterns in what people eat to their microbiomes.”
One big advantage: Feces don’t lie. In reconstructing someone’s diet, people either forget what they ate, fudge the truth, or can’t be bothered to keep track.
“Patients report the fruit they ate yesterday but not the M&Ms,” said Neil Stollman, MD, chief of the division of gastroenterology at Alta Bates Summit Medical Center in Oakland, California.
Some people can’t write it all down because they’re too old or too young — the very people at highest risk of nutrition-associated disease, said David.
Fetching and Figuring Out Feces
It’s a lot of work to collect and analyze fecal matter, for ethical, legal, and logistical reasons. “And then there’s sort of an ick factor to this kind of work,” David said.
To get samples, people place a plastic collection cup under the toilet seat to catch the stool. The person then swabs or scoops some of that into a tube, seals the top, and either brings it in or mails it to the lab.
In the lab, David said, “if the DNA is still inside the plant cells, we crack the cells open using a variety of methods. We use what’s called ‘a stomacher,’ which is like two big paddles, and we load the poop [which is in a plastic bag] into it and then squash it — mash it up. We also sometimes load small particles of what is basically glass into it and then shake really hard — it is another way you can physically break open the plant cells. This can also be done with chemicals. It’s like a chemistry lab,” he said, noting that this process takes about half a day to do.
There is much more bacterial DNA in stool than there is food DNA, and even a little human DNA and sometimes fungi, said David. “The concentration of bacteria in stool is amongst the highest concentrations of bacteria on the planet,” he said, but his lab focuses on the plant DNA they find.
They use a molecular process called polymerase chain reaction (PCR) that amplifies and selectively copies DNA from plants. (The scientists who invented this “ingenious” process won a Nobel Prize, David noted.) Like a COVID PCR test, the process only matches up for certain kinds of DNA and can be designed to be more specific or less specific. In David’s lab, they shoot for a middle ground of specificity, where the PCR process is targeting chloroplasts in plants.
Once they’ve detected all the different sequences of food species, they need to find the DNA code, a time-consuming step. His colleague Briana Petrone compiled a reference database of specific sequences of DNA that correspond to different species of plants. This work took more than a year, said David, noting that only a handful of other labs around the country are sequencing DNA in feces, most of them looking at it in animals, not humans.
There are 200,000 to 300,000 species of edible plants estimated to be on the planet, he said. “I think historically, humans have eaten about 7000 of them. We’re kind of like a walking repository of all this genetic material.”
What Scientists Learn from Fecal DNA
Tracking DNA in digested food can provide valuable data to researchers — information that could have a major impact on nutritional guidance for people with obesity and digestive diseases and other gastrointestinal and nutrition-related issues.
David and Petrone’s 2023 study analyzing DNA in stool samples, published in the Proceedings of the National Academy of Sciences (PNAS), showed what — and roughly how much — people ate.
They noticed that kids with obesity had a higher diversity of plants in them than kids without obesity. Sounds backward — wouldn’t a child who eats more plants be a healthier weight? “The more I dug into it, it turns out that foods that are more processed often tend to have more ingredients. So, a Big Mac and fries and a coffee have 19 different plant species,” said David.
Going forward, he said, researchers may have to be “more specific about how we think about dietary diversity. Maybe not all plant species count toward health in the same way.”
David’s work provides an innovative way to conduct nutrition research, said Jotham Suez, PhD, an assistant professor in the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
“We need to have some means of tracking what people actually ate during a study, whether it’s an intervention where we provide them with the food or an observational study where we let people eat their habitual diet and track it themselves,” said Suez, who studies the gut microbiome.
“Recall bias” makes food questionnaires and apps unreliable. And research suggests that some participants may underreport food intake, possibly because they don’t want to be judged or they misestimate how much they actually consumed.
“There’s huge promise” with a tool like the one described in the PNAS study for making connections between diet and disease, Suez said. But access may be an issue for many researchers. He expects techniques to improve and costs to go down, but there will be challenges. “This method is also almost exclusively looking at plant DNA material, Suez added, “and our diets contain multiple components that are not plants.”
And even if a person just eats an apple or a single cucumber, that food may be degraded somewhere else in the gut, and it may be digested differently in different people’s guts. “Metabolism, of course, can be different between people,” Suez said, so the amounts of data will vary. “In their study, the qualitative data is convincing. The quantitative is TBD [to be determined].”
But he said it might be “a perfect tool” for scientists who want to study indigestible fiber, which is an important area of science, too.
“I totally buy it as a potentially better way to do dietary analytics for disease associations,” said Stollman, an expert in fecal transplant and diverticulitis and a trustee of the American College of Gastroenterology. Stollman sees many patients with diverticular disease who could benefit.
“One of the core questions in the diverticular world is, what causes diverticular disease, so we can ideally prevent it? For decades, the theory has been that a low fiber diet contributes to it,” said Stollman, but testing DNA in patients’ stools could help researchers explore the question in a new and potentially more nuanced and accurate way. Findings might allow scientists to learn, “Do people who eat X get polyps? Is this diet a risk factor for X, Y, or Z disease?” said Stollman.
Future Clinical Applications
Brenda Davy, PhD, is a registered dietitian and professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech. She conducts research investigating the role of diet in the prevention and treatment of obesity and related conditions such as type 2 diabetes. She also develops dietary assessment methods. More than a decade ago, she developed one of the first rapid assessment tools for quantifying beverage intake — the Beverage Intake Questionnaire — an assessment that is still used today.
“Dietary assessment is necessary in both research and clinical settings,” Davy said. “If a physician diagnoses a patient with a certain condition, information about the patient’s usual dietary habits can help him or her prescribe dietary changes that may help treat that condition.”
Biospecimens, like fecal and urine samples, can be a safe, accurate way to collect that data, she said. Samples can be obtained easily and noninvasively “in a wide variety of populations such as children or older adults” and in clinical settings.
Davy and her team use David’s technology in their work — in particular, a tool called FoodSeq that applies DNA metabarcoding to human stool to collect information about food taxa consumed. Their two labs are now collaborating on a project investigating how ultraprocessed foods might impact type 2 diabetes risk and cardiovascular health.
There are many directions David’s lab would like to take their research, possibly partnering with epidemiologists on global studies that would help them expand their DNA database and better understand how, for example, climate change may be affecting diet diversity and to learn more about diet across different populations.
A version of this article appeared on Medscape.com.
Are ants the future of cancer detection?
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.
Cancer diagnosis is frightening, invasive, time-consuming, and expensive. And more than 1.6 million people get that cancer diagnosis every year in the United States. That’s a lot of biopsies and a lot of looking at cells under highly sensitive microscopes.
But imagine if detecting cancer in those samples was as simple as taking a whiff.
We know some animals – like dogs and mice – have very sensitive noses that can sniff out disease. Inspired by those studies, French scientists decided to explore whether ants – known for their olfactory prowess – could do the same.
“Using olfaction to detect diseases is not a novel idea,” says Baptiste Piqueret, PhD, a researcher at Sorbonne Paris Nord University and lead author of the study. “Knowing how well ants can learn and how they use olfaction, we tested the abilities of ants to learn and detect diseases.”
While this is still far away from real-life clinical use, it could one day lead to a cheaper, more accessible (if not a little weird) alternative for detecting cancer. What would this new diagnostic method look like?
Pavlov’s ant
Cancer cell metabolism produces volatile organic compounds (VOCs) – organic chemicals that smell and can serve as biomarkers for diagnosis.
To train the ants to target VOCs, the researchers placed breast cancer cells and healthy cells in a petri dish – but the cancer cells included a sugary treat. “We associated a reward to the smell of cancer,” Dr. Piqueret says.
It’s a technique scientists call classical, or Pavlovian, conditioning. A neutral stimulus (cancer smell) is associated with a second stimulus (food) that elicits a behavior. After doing this a few times, the ant learns that the first stimulus predicts the second, and it will seek out the odor hoping to find that food.
Once the training was complete, the researchers presented the ant with the learned odor and a novel one – this time without a reward. Sure enough, the ants spent more time investigating the learned odor than the novel one.
“If you are hungry and you smell the odor of fresh bread, you will enter the closest bakery,” says Dr. Piqueret. “This is the same mechanism the ants are using, as you learned that fresh bread odor equals food.”
Dogs can detect VOCs via the same technique but take months and hundreds of trials to condition, the researchers note. F. fusca ants learn fast, requiring only three training trials.
Why ants?
Ants communicate primarily through olfaction or scent, and this sophisticated “language” makes them very sensitive to odors.
“Since ants are already well-attuned to detecting different chemicals, this makes them ideal for scent recognition,” says Corrie Moreau, PhD, an evolutionary biologist and entomologist at Cornell University, Ithaca, N.Y.
In their tiny ant worlds, the little creatures use chemicals, called pheromones, to convey information to other members of their nest.
“There are alarm pheromones to signal an intruder, trail pheromones so an ant knows which way to walk to a food source, and colony-level odors that signal another ant is a member of the same colony,” Dr. Moreau says.
But on closer inspection, you won’t see a nose on an ant. They “smell” with their antennas.
“These specialized structures are covered with highly sensitive receptors to be able to discern even small chemical differences,” Dr. Moreau says.
There are over 14,000 species of ants and as far as scientists like Dr. Moreau know, all of them use chemical communication, though some are better than others at detecting compounds, such as those scientists are interested in using to detect disease.
Diagnostic ants: Realistic or a curiosity?
Whether or not the new research findings could lead to a real tool for diagnosing cancer is difficult to say, says Dr. Moreau. The study only focused on pure cancer cells in a lab and not those growing inside a human body.
Anna Wanda Komorowski, MD, a medical oncologist-hematologist at Northwell Health in New York, found the study interesting and was impressed with how the researchers trained the ants. But she notes more research would be needed to parse out things like how long the ants would remember their training, and how long they could be kept in a lab for testing.
One of the attractive aspects of the research is that if it worked it might be a cheaper alternative to normal lab practices for detecting cancer cells, and possibly useful in some low-income settings where labs do not have access to cell stain technologies used to detect cancer cells.
Another glitch with the study, notes Dr. Komorowski: “The cells we’d expose them to probably would not be the same cells as those used in the study. They exposed the ants to live cell cultures. Usually, we collect material from biopsy and drop it into formaldehyde, which has such a strong odor. So the lab protocol for cancer detection would have to be different. It could be kind of tricky.”
And while ants are cheaper than stains and dyes and formaldehyde, you’d have to hire someone to train the ants – there’d still be a human factor and related costs.
“It would take much more research to figure out cost, and how applicable and reproducible it would be,” Dr. Komorowski says.
And then there’s the question of whether the ants would do their cancer-detecting work in the lab only, or if direct patient interaction might lead to a diagnosis more swiftly.
Ant expert Dr. Moreau adds, “The human body emits many other odors, so the question is whether the ants would be able to ignore all the other scents and focus only on the target scent.”
“But these results are promising,” she continues. “I guess the question is whether a patient would be willing to have trained ants crawl all over their body looking for potential cancer cells.”
A version of this article first appeared on WebMD.com.