Genetic Study Connects Vitamin B1 Metabolism to Gut Motility, IBS Risk - Video

A new study published in Gut sheds light on how genetics and vitamin B1 metabolism influence gut motility, offering potential new treatment targets for common digestive disorders like irritable bowel syndrome (IBS).

The research focused on stool frequency (SF) as a practical proxy for gastrointestinal (GI) motility, which is essential for nutrient absorption, waste elimination, and overall digestive health. Disrupted motility underlies conditions ranging from constipation-predominant IBS to diarrhea-predominant IBS, yet treatments are often limited due to an incomplete understanding of underlying mechanisms.

Researchers analyzed data from 268,606 participants across six biobanks, including five European and one East Asian population. Genetic analysis identified 479 significant variants across 18 genomic regions, corresponding to 21 independent genetic signals and 197 protein-coding genes. Notably, three variants were highlighted: rs12407945 (Europeans), rs2581260, and rs12022782 (multi-ancestry).

The top variant affects SLC35F3, a gene transporting vitamin B1 (thiamine) into cells, while another affects XPR1, a phosphate exporter needed to activate thiamine into thiamine pyrophosphate. These findings suggest that the way the body processes vitamin B1 plays a key role in regulating gut motility through interactions between the enteric and central nervous systems.

Observational data from 98,449 participants further supported this link: higher thiamine intake was associated with increased SF, with effects depending on an individual’s genetic variants. Other genes implicated include KLB, which regulates bile acid metabolism, and COLQ, involved in gut nerve signaling and linked to diverticular disease risk.

Drug signature analysis highlighted 831 compounds that could theoretically modulate gut motility, offering avenues for repurposing medications or developing new interventions. While stool frequency is a proxy measure and dietary thiamine intake was observational, these findings uncover a previously underappreciated role for vitamin B1 in bowel regulation and pave the way for mechanistic and clinical studies to improve treatments for motility disorders.

REFERENCE: Díaz-Muñoz C, Bozzarelli I, Lopera-Maya EA, et al. (2026) Genetic dissection of stool frequency implicates vitamin B1 metabolism and other actionable pathways in the modulation of gut motility. Gut. DOI: 10.1136/gutjnl-2025-337059. https://gut.bmj.com/content/early/2026/01/05/gutjnl-2025-337059