Bowel habits aren’t exactly table talk. But they reflect how quickly the gut moves things along, and when that goes wrong, people can experience constipation, diarrhea or irritable bowel syndrome (IBS). However, the biological mechanisms that control bowel movements are not yet fully understood. A new study, published today in Intestinereports DNA evidence for intestinal motility and points to the biology of vitamin B1 (thiamine) as an unexpected avenue for further research.
An international team coordinated by Mauro D’Amato, professor of Medical Genetics at LUM University, and Research Professor Ikerbasque at CIC bioGUNE, member of BRTA, used a large-scale genetic approach to look for common differences in DNA associated with how often people open their bowels (referred to in the study as stool frequency). They studied questionnaires and genetic data from 268,606 people of European and East Asian descent and used computational analyzes to identify which genes and mechanisms were most likely involved.
The analysis identified 21 regions of the human genome that influence the frequency of bowel movements, including 10 that had not been reported before. Several of the genetic signals pointed to pathways and mechanism already known to affect gut motility, which was reassuring because it means the results align with biology that makes sense. For example, the study highlighted bile acid regulation (bile acids help digest fats and also act as signaling molecules in the gut) and nerve signaling associated with intestinal muscle contractions (including signaling associated with acetylcholine, which helps nerves communicate with muscles).
But the most striking result came when the team narrowed their findings to two high-priority genes that converge on vitamin B1 biology, namely genes linked to how thiamine is transported and activated in the body (SLC35F3 and XPR1). To investigate whether this vitamin B1 signal shows up in real-world data, the researchers next turned to additional nutritional information from the UK Biobank. In 98,449 participants, they found that higher dietary thiamine intake was associated with more frequent bowel movements. Importantly, the relationship between thiamine intake and frequency of bowel movements differed according to an individual’s genetic makeup at the SLC35F3 and XPR1 genes (analyzed together as a combined genetic score). In other words, the data suggest that inherited differences in thiamine handling may influence how vitamin B1 intake relates to bowel habits in the general population.
We used genetics to build a road map of biological pathways that determine gut rhythm. What stood out was how strongly the data implicated vitamin B1 metabolism alongside established mechanisms such as bile acids and nerve signaling.”
Dr. Cristian Diaz-Muñoz, first author of the study
The study also supports a significant biological overlap between frequency of bowel movements and IBS, a common condition affecting millions of people worldwide. “Bowel motility problems are at the heart of IBS, constipation and other common bowel motility disorders“says Professor Mauro D’Amato,”but the underlying biology is very difficult to determine. These genetic results highlight specific pathways, particularly vitamin B1, as testable leads for the next stage of research, including laboratory experiments and carefully designed clinical studies..”
The study was conducted by Mauro D’Amato’s Gastrointestinal Genetics Research Group and involved researchers from CIC bioGUNE in Spain, LUM University, Institute of Genetics and Biomedical Research – CNR, CEINGE and University of Naples Federico II in Italy, University of Groningen in the Netherlands, University of UK Research Institute, University of Cantario in Oxfordia. Canada and Monash University in Australia. The research was supported by grants from MCIU/AEI/10.13039/501100011033 and ERDF/EU (PID2023-148957OB-I00). PRIN2022/NextGenerationEU (2022PMZKEC; CUP E53D23004910008 and CUP B53D23008300006); ERC Starting Grant (101075624); PNRR/NextGenerationEU (PE00000015/Age-it); NWO-VICI (VI.C.232.074); NWO Gravitation ExposomeNL (024.004.017); EU Horizon DarkMatter Program (101136582).
