By Betty Zou
If you’ve ever listened to a group of preschoolers or elementary-school kids bantering on the playground, chances are you will have heard the word “poop” — and various creative iterations of it — more times than you can count.
But somewhere between childhood and adulthood, we stop talking about poop. We’re taught that bowel movements are not an appropriate topic for polite conversation, and we worry that bringing it up might make us look crass or ill-mannered. As the bestselling children’s book by Japanese author Taro Gomi teaches us, everyone poops. However, not everyone is ready to talk about it.
“There is social stigma against talking about bowels and excrement, and this stigma is particularly significant in more conservative communities, among women and among older people,” says Laura Targownik, the director of the Division of Gastroenterology and Hepatology at the University of Toronto’s Temerty Faculty of Medicine.
Targownik is a gastroenterologist at Sinai Health who sees patients experiencing gastrointestinal issues, including people with inflammatory bowel disease (IBD). She says that while many people would not hesitate to discuss changes in their vision or a new pain in their knee with their family and friends, they feel reticent bringing up concerns about bloating, stool consistency and passing gas. And by not talking about these concerns, they miss out on an opportunity to get reassurance and have their experiences validated.
“The concerns about stigma and fear are real, and it does delay care,” says Targownik.
The taboo around bowel movements — their frequency, sensation and appearance — stems in part from an evolutionary strategy to avoid infectious diseases transmitted through feces. But for all the discomfort some people feel in talking about poop, researchers and clinicians hold an equal amount of excitement around poop’s potential as a tool to improve health.
Laura Targownik / Photo by Julia Soudat
There is social stigma against talking about bowels and excrement
Plumbing the mysteries of the gut microbiome
The promise of poop stems from its association with the gut microbiome, a complex ecosystem of bacteria, viruses, fungi and other micro-organisms living in our intestines. As a byproduct of the gastrointestinal system, fecal matter contains a rich sampling of gut microbes, both dead and alive.
Researchers have long known about the existence of the gut microbiota, but it was only in the past two decades that technological advances in DNA sequencing have allowed us to catalogue the different bacteria found in our gut — by sequencing the micro-organisms in our stool.
“Next-generation sequencing techniques became available that allowed us to see which bacteria were present and what they were doing, without needing to isolate them in the lab,” says Elena Comelli, a professor of nutritional sciences at Temerty Medicine.
Today, the gut microbiome has been linked to an ever-growing list of health conditions, including autoimmune disorders, cancer, cardiovascular disease, mental health and neurodevelopmental conditions. Perhaps unsurprisingly, the potential of poop is greatest in areas related to gut health.
For example, the research of Temerty Medicine Department of Immunology Professor Dana Philpott (PhD ’97) has uncovered new insights into how the gut microbiome shapes immune responses in the gut and how disruptions in these pathways can contribute to metabolic and gastrointestinal health and disease.
One of the techniques her lab uses to study these topics is fecal microbiota transplantation (FMT), a procedure in which stool containing gut microbes from a healthy donor is transplanted into a recipient: in Philpott’s case, germ-free mice that lack a native gut microbiota. As a research technique, FMT allows researchers to directly interrogate the cause-and-effect relationship between the gut microbiome and specific health conditions. As a therapy, FMT can modify a person’s gut microbiome to potentially prevent, manage and treat illness.
From waste to remedy
Currently, the only evidence-backed clinical indication for FMT is as a treatment for recurrent gastrointestinal infections caused by the bacterium Clostridioides difficile. University Health Network (UHN) is one of only two hospitals in Ontario with a formal program to perform FMT. Susy Hota (MD ’02, PGME ’06, PGME ’07, MSc ’11) co-leads a team of clinical and research staff to offer this highly effective and often curative treatment to patients experiencing persistent C. difficile infections.
Hota is the division head for infectious diseases at UHN and Sinai Health and an associate professor in the Department of Medicine at Temerty Medicine. She also serves as the clinical lead and co-principal investigator of the Microbiota Therapeutics Outcomes Program (MTOP), a collaborative multidisciplinary research program supported by U of T, UHN and Sinai Health.
MTOP was established in 2015 with three goals: to standardize and improve FMT protocols, to create a platform to support robust clinical studies, and to understand the long-term health impacts of FMT. One of the research projects supported by MTOP examined the effects of FMTs from healthy lean donors on insulin resistance and other obesity-related characteristics in people with severe obesity.
“There’s been plenty of evidence, particularly based on animal models, where obesity was transferable with FMT in germ-free mice,” says Johane Allard (PGME ’89), a clinician-scientist at UHN and a professor of medicine and nutritional sciences at Temerty Medicine.
In 2022, Allard and her colleagues published results from a randomized controlled trial of FMT in people with obesity. Twenty-eight recipients with severe obesity were randomly assigned to receive a fecal transplant of their own stool or a stool from a healthy lean donor.
“FMT [with healthy donor stool] did not have a significant effect in improving metabolic parameters, but we saw improvements in the microbiome and more beneficial interactions between the microbiome and metabolites,” says Allard.
She notes that patients who received a donor transplant also had lower levels of LDL cholesterol — the so-called “bad cholesterol” — less hunger and sweet cravings, decreased anxiety and depression, and improved emotional well-being and energy levels.
In a follow-up study, Allard, Philpott, Hota, UHN senior scientist Herbert Gaisano and colleagues performed FMTs on mice using stool from people before and after they had gastric bypass surgery. The researchers found that surgery-induced changes in the gut microbiota could directly improve metabolism in mice through higher energy expenditure from increased brown fat mass and activity, and reduced fat accumulation in the fatty liver.
To move the FMT field forward, Allard says several fundamental questions still need to be addressed. For example, how many doses of FMT are appropriate? While a single transplant is enough to treat most cases of C. difficile infections, other conditions may require multiple transplants.
“You have to think about what is the best mode of delivery to have the best effect. Are you going to modify the diet to sustain that good microbiome?” she asks. Answering these questions will require human studies, but Allard thinks that with new medications like GLP-1 agonists, people will be less interested in FMTs as a potential strategy to manage weight and metabolic conditions. “Right now, it might be more difficult to recruit patients for an FMT trial [for obesity],” she says.
Bryan Coburn
As an infectious disease specialist, I looked around and saw all of these populations where their gut microbiome is an ecological wasteland
When microbes become medicine
Beyond gut-related illnesses, there is growing evidence that the intestinal microbiota can influence the onset and progression of many other chronic health conditions. As an example, Professor Heather Reich (PGME ’02, PhD ’07), director of Temerty Medicine’s Division of Nephrology and clinician-scientist at UHN, and Temerty Medicine Department of Immunology Professor Jen Gommerman (PhD ’98) are collaborating to study how the microbiome contributes to the aberrant immune responses that drive IgA nephropathy, an important cause of kidney failure.
For Comelli, the gut-breast axis has been a particularly exciting area of focus for her group. Specifically, the researchers are looking at how the gut microbiota mediates the beneficial effects of flaxseed on breast cancer prevention and treatment. Flaxseed contains compounds called lignans that are broken down by gut microbes into estrogen-like molecules. Once produced, these plant-derived estrogens are absorbed into the intestinal cells and circulated throughout the body to various organs, including the breast.
In 2024, Comelli and her team published a study on pubertal mice that examined the connection between the gut microbiota, flaxseed and short snippets of RNA, called microRNA, found in the mammary gland.
“We found that there was a relationship between which bacteria are in the gut and which microRNAs are expressed in the mammary gland,” she says. “The microRNAs were important for oncogenic [or cancer-promoting] pathways, and we found that with flaxseed, we could modify these relationships to be more anti-oncogenic.”
Comelli says that adolescence is a critical window during which the gut microbiome shifts toward a more permanent, adult-like state. Her research highlights the potential of flaxseed supplementation during this key developmental stage as a way to leverage the capabilities of the gut microbiome to reduce breast cancer risk. Still other researchers are pursuing the use of microbiome-targeting therapies to improve outcomes in people with cancer.
Bryan Coburn (PGME ’12, PGME ’13), a clinician-scientist and infectious diseases physician at UHN who studies the role of the human microbiome in health and disease, recalls the moment when he started paying attention to the potential of FMTs to enhance a person’s response to cancer immunotherapy.
“Three papers came out in tandem in 2018 showing that in humans, microbiome compositional differences between responders and non-responders were observed in multiple independent cohorts,” says Coburn, an associate professor in the Departments of Medicine, Immunology, and Laboratory Medicine and Pathobiology at Temerty Medicine.
The studies also showed that immunotherapy response was a trait that could be transferred via FMTs to germ-free or antibiotic-treated mice. A self-described enthusiastic early adopter, Coburn recognized the need for an intervention that was more scalable and easier to administer than fecal transplants. The alternative, Coburn and his collaborators thought, could be oral supplements that contained complex, lab-grown mixtures of stool-derived bacteria from healthy donors.
Coburn teamed up with Anna Spreafico, an associate professor at Temerty Medicine’s Department of Medicine and a clinician-investigator at UHN’s Princess Margaret Cancer Centre, to study the ecological and immunological impacts of one such supplement called MET4. It contains 30 species of bacteria associated with immunotherapy response in people with advanced cancer.
Their results showed that some people who took the supplement had modest changes in their gut microbiome and developed antibodies against the MET4 bacteria, highlighting the supplement’s potential to stimulate the immune system. Coburn says that while the findings were less dramatic than he had hoped, they encouraged him to reorient his research program to focus on patients for whom FMTs and microbiome-targeting therapies are likely to have the biggest impact.
“As an infectious disease specialist, I looked around and saw all of these populations where their gut microbiome is an ecological wasteland,” he says. These include people whose microbial communities have been continually disrupted by frequent antibiotic use and those undergoing transplants. Coburn’s experience with MET4 also highlighted another important reality: In gut microbiome and FMT research — as in many other areas of biomedical research — exciting results in mouse models often fail to replicate in humans. And even when they do, the effects are rarely as large or meaningful.
Banking on stool
One of the challenges with doing large-scale, robust human studies of FMT is maintaining a high-quality stool bank. Hota says stigma is not a barrier when it comes to recruiting donors, but potential universal stool donors need to pass rigorous and strict screening tests and must commit to providing stool donations three to five times a week for her program. According to a report published by Hota and her MTOP colleagues in 2019, out of 322 prospective donors screened in the program’s first two years, only five passed full screening, and only two became active donors.
Funding is also an issue. Because FMT is still considered an experimental treatment, transplants — even to treat C. difficile infections — are not covered by public funding and rely entirely on research grants and in-kind support provided by hospitals. Hota estimates that her team at UHN performs only about 10 to 15 fecal transplants each year because of funding and capacity constraints.
“We have, unfortunately, a substantial wait list because we don’t have the capacity to keep up,” she says.
Researchers have tried to circumvent these challenges by developing alternatives to FMTs — such as the oral supplement MET4 — that are easier to manufacture and administer. But these synthetic bacterial cocktails often cannot capture the full complexity of a stool sample, which also contains metabolites and, as Comelli’s work has recently shown, microRNAs connected to the microbiota.
For a field still in its nascency, sustaining public interest and securing stable support will allow researchers to continue their efforts to find solutions to answer the questions and overcome the hurdles related to FMTs.
“I can’t wait to see what happens over the next 10 years with clinical trials and microbiome-targeting therapies,” says Coburn. Meanwhile, clinicians like Targownik are continuing to try to normalize and create safe spaces for conversations about bowel health.
In a country with one of the highest rates of IBD in the world, stigma around discussing poop can have harmful consequences, she says. She sees many people who put off going to see the doctor because they feel a sense of shame and responsibility that their illness was caused by something they did or ate.
“To what extent do we incorporate poop education into our curriculum in schools and in culture?” asks Targownik.
“Even things like the poop emoji have demystified it by making poop cute and something that people talk about.” 💩