Although discussions about bowel habits are often avoided, they provide crucial information regarding the effectiveness of the digestive system’s ability to transport materials through the intestines. Disruptions in this mechanism can result in conditions such as constipation, diarrhea, or irritable bowel syndrome (IBS). Despite their commonality, the precise biological mechanisms governing bowel movements remain incompletely understood. A recent investigation, published on January 20 in the journal Gut, delivers novel genetic insights into intestinal motility and unexpectedly highlights vitamin B1, also known as thiamine, as a promising avenue for additional exploration.
International Team’s Large-Scale Genetic Analysis
This research was spearheaded by an international collaboration under the leadership of Mauro D’Amato, who holds the position of Professor of Medical Genetics at LUM University and serves as an Ikerbasque Research Professor at CIC bioGUNE, part of the BRTA network. The team employed a comprehensive genetic approach to pinpoint common DNA variations associated with the frequency of bowel movements, termed stool frequency in the study. They examined genetic information alongside health survey responses from 268,606 participants of European and East Asian descent. By leveraging sophisticated computational techniques, the scientists determined the genes and biological pathways most closely tied to gastrointestinal transit.
Validation Through Established Gut Mechanisms
The genomic examination revealed 21 distinct regions in the human genome that impact the regularity of bowel movements, with 10 of these loci representing entirely new discoveries. A significant portion of these genetic markers aligned with well-documented systems that control intestinal activity, which bolsters confidence in the study’s reliability and consistency with prior scientific understanding. Key among these were pathways for bile acid management—where bile acids facilitate fat breakdown and serve as signaling agents within the intestines—and neural pathways that trigger contractions in the gut muscles, particularly those involving acetylcholine-mediated communication between nerves and smooth muscle tissues. Collectively, these observations solidify and expand upon the foundational principles of gut physiology.
Unexpected Prominence of Vitamin B1 Pathways
The standout revelation came during a deeper dive into two pivotal genes associated with vitamin B1 metabolism: SLC35F3 and XPR1. These genes are instrumental in the transportation and activation processes of thiamine throughout the body. To assess whether this genetic association manifested in real-world behaviors, the researchers scrutinized dietary records from the UK Biobank database, encompassing 98,449 individuals. The data indicated that elevated consumption of thiamine from food sources correlated with increased bowel movement frequency.
However, this correlation was not consistent for everyone. The influence of thiamine consumption on stool frequency varied based on genetic polymorphisms in the SLC35F3 and XPR1 genes, evaluated as an integrated genetic risk score. Such findings imply that hereditary variations in thiamine processing could modulate how dietary vitamin B1 affects an individual’s bowel regularity across diverse populations.
Implications for IBS and Directions for Future Studies
Dr. Cristian Diaz-Muñoz, the lead author of the study, remarked, “Through genetic analysis, we have constructed a detailed map of the biological pathways dictating the rhythm of gut motility. Particularly striking was the robust evidence linking vitamin B1 metabolism to these processes, in tandem with recognized factors like bile acids and neural signaling.”
Furthermore, the results establish a substantive biological tie between stool frequency and IBS, which impacts millions globally. Professor Mauro D’Amato elaborated, “Disorders of gut motility are central to IBS, chronic constipation, and various other prevalent gastrointestinal conditions, yet unraveling their biological roots proves challenging. Our genetic discoveries spotlight targeted pathways, notably vitamin B1-related ones, as prime candidates for subsequent investigations, encompassing laboratory validations and meticulously planned clinical trials.”
The project was coordinated by Mauro D’Amato’s Gastrointestinal Genetics Research Group, with contributions from researchers at CIC bioGUNE in Spain, LUM University, the Institute for Genetics and Biomedical Research – CNR, CEINGE, and the University of Naples Federico II in Italy, the University of Groningen in the Netherlands, the University of Oxford in the United Kingdom, Concordia University and the Ontario Institute for Cancer Research in Canada, and Monash University in Australia. Funding was provided by various grants, including those 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), and the EU Horizon DarkMatter program (101136582).
