A landmark international study uncovers surprising new clues about what controls gut health and why a common vitamin may hold the key.

Millions of people live with the daily disruption of Irritable Bowel Syndrome (IBS): the cramping, the unpredictability, the exhausting cycle of constipation and diarrhea. For too long, the medical advice has been frustratingly vague: monitor the foods you eat, drink more water, increase your fibre intake, manage your stress, try this medication…

Now, a major new international study published in the journal Gut suggests the real answers may be written in our DNA. And that a vitamin most of us have never thought twice about could be a key part of the story.

The study involved over 268,606 people from around the world. It identified 21 regions of the human genome linked to how often people have bowel movements. This measure is important to gauge how fast food moves through the digestive system. The researchers found two genes involved in how the body absorbs and activates Vitamin B1 (thiamine) that play a meaningful role in gut motility. People who consumed more Vitamin B1 tended to have more regular bowel movements. And that relationship was shaped by which version of these genes a person carried.

“The study highlights a previously unrecognized role for vitamin B1 metabolism in controlling gut motility,” says Dr. Marie-Julie Favé, a co-author on the study. At the time of the research, Favé was a postdoctoral researcher at the Université de Montréal and the Ontario Institute for Cancer Research, and is now an Associate Professor at Concordia University. “This means that how our bodies process vitamin B1, influenced by specific genes, can affect how quickly or slowly food moves through our digestive system.”

Nearly double the genetic clues

Before this research, scientists had identified roughly a dozen genetic regions linked to gut motility. This study nearly doubles that number. Several of the newly discovered genes are involved in nerve signalling in the gut or the network of neurons sometimes called the “second brain.” Others are tied to bile acid production, which helps regulate how fast food travels through the colon.

The study also confirmed something many IBS patients have long felt to be true: that gut health and mental health are connected at the level of DNA. “It confirms that stool frequency shares genetic connections with various gastrointestinal disorders like IBS and even psychiatric conditions like anxiety and depression,” says Favé. “This reinforces the concept of the gut-brain axis, suggesting that gut health and mental well-being are deeply intertwined at a genetic level.”

Perhaps most unexpectedly, several gut motility genes overlapped with genes linked to blood pressure and heart disease. It’s a reminder that the body’s systems are more interconnected than they might appear on the surface.

Where this research points next

These new findings add to a list of associated genes and point toward biological mechanisms that are genuinely actionable. The thiamine pathway involves transporters that could be targeted by existing or novel drugs, and a dietary component that can be measured, modified, and studied in clinical trials. Several other compounds identified through the study’s drug signature analyses, like medications already used for cardiovascular conditions, warrant investigation for their effects on gut motility.

For the research community, the study also makes a methodological case worth noting. Using stool frequency as a measurable stand-in for gut motility allowed researchers to work at a scale that direct clinical measurement never could. The 21 genetic signals identified here far exceed the six risk regions uncovered in the largest IBS genome-wide study to date. It suggests that endophenotypes like stool frequency may be among the most productive tools available for unpacking the genetics of functional gastrointestinal disorders.

The authors are calling for mechanistic and clinical follow-up, particularly around thiamine supplementation in genetically susceptible individuals. As Favé notes: “Additional support for follow-up mechanistic and clinical trials will accelerate the translation of these genetic insights into tangible health benefits, offering new hope for individuals suffering from IBS and other gut motility disorders.”

The Canadian connection

None of this would have been possible without the sustained generosity of research participants, including the Canadians involved in CanPath. This study drew on data from the Global Biobank Meta-Analysis Initiative (GBMI), a network of 23 biobanks from four continents representing over 2.2 million people. CanPath, and specifically the Ontario Health Study, Canada’s representative in the GBMI, is part of that network.

Dr. Favé and fellow co-author Dr. Philip Awadalla, both are part of the Canadian team whose work made this contribution possible.

“This work is a testament to the immense value of large-scale, long-term cohort participation,” says Awadalla, CanPath National Scientific Co-Director. “Without the vast amount of genetic and health data provided by volunteers, discoveries like the critical role of vitamin B1 metabolism in gut motility would not be possible.”

If you have ever filled out a health questionnaire or donated a sample as part of a long-term study, you may have played a quiet but real role in this discovery.

“To study participants, funders, and collaborators: Your contributions were absolutely essential,” reflects Favé. “Without the vast amount of genetic and health data you provided, discoveries like the critical role of vitamin B1 metabolism in gut motility would not be possible.”

Somewhere in that data is a contribution that brings us closer to real answers for the millions of people living with IBS. This is what it looks like when science is built by and for all of us.

For more information, please contact:

Megan Fleming
Communications & Knowledge Translation Officer
Canadian Partnership for Tomorrow’s Health (CanPath)
info@canpath.ca