Published in Gut and involving over 268,000 individuals, the study found intestinal motility is a heritable trait, with some people genetically predisposed to a ‘lazy gut’.
The researchers from academic institutions across Europe, Australia and Canada discovered these individuals often have a reduced response to thiamine: a vitamin which appears to play a crucial role in gut motility.
Lead author Dr. Mauro D’Amato said the study opens up opportunities for further research into whether thiamine supplementation can alleviate disordered gut motility and IBS symptoms in genetically susceptible individuals.
“[We uncovered] both known (bile acids and acetylcholine, reassuring our strategy was meaningful) and entirely new pathways like vitamin B1,” he told NutraIngredients. “The latter in particular was not linked to gut motility before, and our findings tell us that vitamin B1 biology may be important in controlling peristalsis, with potential to alleviate constipation. This creates opportunities for translational applications including animal testing and human clinical trials.”
Uncovering new pathways driving slow gut motility
Constipation is a common issue, estimated to affect approximately one in seven adults worldwide. Often, it is caused by reduced gut motility, or slow gut transit time, leading to hardening of the stool and infrequent bowel movements.
Previously, reduced gut motility was thought to be caused primarily by lifestyle factors such as low fiber and fluid intake. However, this new research suggests that genetics also play a key role.
Through performing a genome-wide association study (GWAS) and scanning millions of genetic markers, the researchers identified two genes, one which acts as a thiamine transporter and another which helps to convert thiamine into its active form, thiamine pyrophosphate (TPP).
Genetic variations in these two genes were found to negatively impact intracellular levels of thiamine and phosphate leading to a biological impact on stool frequency.
“While we still do not know the exact mechanisms, it is likely to involve the communication across neurons via acetylcholine-related metabolism and the neurotransmitters network, ultimate leading to modulatory effects on peristalsis,” Dr. D’Amato said.
The researchers further confirmed their findings by analyzing dietary data from more than 98,000 UK Biobank participants. This data showed a significant association between thiamine intake and gut motility, with higher thiamine dietary levels correlating with increased stool frequency.
Dr. D’Amato said the discovery of thiamine as a modulator of gut motility is an important novel finding, which has only scarcely been highlighted in previous scientific literature.
“The vitamin B1 we consume may be more effective in some people compared to others (in terms of contributing to bowel movement), because of their respective genetic profiles,” he said. “This is still indirect evidence, but it should stimulate experimentation in animal models (mice treated with vitamin B1 for example) and/or well-designed clinical trials, to verify whether direct administration of vitamin B1 (with supplements or via dietary changes) has an effect on gut motility, increasing the frequency of bowel movements and relieving IBS and/or constipation.”
Gut motility may be linked to heart and mind health
The large, multi-ancestry study also showed that stool frequency shares genetic architecture with gastrointestinal, psychiatric and cardiovascular traits.
By performing large-scale statistical comparisons across hundreds of different conditions, the researchers calculated genetic correlations across different domains.
Stool frequency was found to be significantly linked with anxiety, depression, and bipolar (likely due to the gut-brain axis), as well as hypertension and angina, suggesting those with chronic constipation may be at higher risk of cardiovascular events.
While the authors acknowledge the study’s limitations, including a reliance on self-reported stool frequency data and a lack of data on dietary, medication or lifestyle variables, they say the research confirms previous evidence which links gut health to neurological and cardiovascular pathways.
“Importantly, we uncover a previously unrecognized role for vitamin B1 (thiamine) in gut motility, highlighting a biologically plausible and modifiable axis with potential for nutritional or pharmacological intervention,” they wrote. “Together, these findings provide a strong rationale for investigating and repurposing compounds that target genetically implicated, tractable pathways, warranting further mechanistic and clinical studies, particularly in the context of IBS and other dysmotility syndromes.”
Source: Gut. doi: 10.1136/gutjnl-2025-337059. “Genetic dissection of stool frequency implicates vitamin B1 metabolism and other actionable pathways in the modulation of gut motility.” Authors: C. Díaz-Muñoz, et al.
