New genetic insights reveal vitamin B1's role in gut health and motility

Bowel habits aren't exactly dinner-table talk. But they reflect how quickly the gut moves things along, and when that goes wrong people can experience constipation, diarrhoea, or irritable bowel syndrome (IBS). Yet the biological mechanisms that control bowel movements are still not fully understood. A new study, published today in Gut, reports DNA clues to intestinal motility and spotlights vitamin B1 (thiamine) biology as an unexpected pathway for follow-up research.

An international team coordinated by Mauro D'Amato, Professor of Medical Genetics at LUM University and Ikerbasque Research Professor at CIC bioGUNE, member of BRTA, used a large-scale genetics approach to search for common DNA differences associated with how often people open their bowels (referred to in the study as stool frequency). They studied questionnaire and genetic data from 268,606 people of European and East Asian ancestry and used computational analyses to pinpoint which genes and mechanisms are most likely involved.

The analysis identified 21 regions of the human genome influencing bowel movement frequency, including 10 that had not been reported before. Several of the genetic signals pointed to pathways and mechanism already known to affect gut movement, 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 signalling molecules in the gut) and nerve signalling relevant to intestinal muscle contractions (including acetylcholine-related signalling, which helps nerves communicate with muscle) 

But the most striking result emerged when the team narrowed down their findings to two high-priority genes converging on vitamin B1 biology, specifically genes linked to how thiamine is transported and activated in the body (SLC35F3 and XPR1). To explore whether this vitamin B1 signal shows up in real-world data, the researchers then turned to additional dietary information from 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 bowel movement frequency differed depending on a person's genetic makeup at the SLC35F3 and XPR1 genes (analysed 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 roadmap of biological pathways that set the gut's pace. What stood out was how strongly the data pointed to vitamin B1 metabolism, alongside established mechanisms like bile acids and nerve signaling." 

Dr. Cristian Diaz-Muñoz, first author of the study

The study also supports a meaningful biological overlap between bowel movement frequency and IBS, a common condition affecting millions worldwide. "Gut motility problems sit at the heart of IBS, constipation and other common gut-motility disorders" says Prof Mauro D'Amato, "but the underlying biology is very hard to pin down. These genetic results highlight specific pathways, especially vitamin B1, as testable leads for the next stage of research, including lab experiments and carefully designed clinical studies."

The study was led by Mauro D'Amato's Gastrointestinal Genetics Research Group and involved investigators from CIC bioGUNE in Spain, LUM University, Institute for Genetics and Biomedical Research – CNR, CEINGE and University of Naples Federico II in Italy, University of Groningen in The Netherlands, University of Oxford in UK, Concordia University and Ontario Institute for Cancer Research in 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).