Gut Microbiome Response to the Reduction of Diet Induced Obesity by Vitamin B₁ Supplementation

Dietary deficiencies in vitamins such as thiamine (Vitamin B1) produce a range of deleterious health effects and can occur even in developed countries. We’ve hypothesized that a physiological deficiency in thiamine can exacerbate conditions like obesity, diabetes, and fatty liver that are associated with consumption of high fat diets rich in soybean oil (SO) and that one or more of these conditions might be associated with changes in the composition of the gut microbiota. We first evaluated the short-term effect of thiamine deficiency on the gut microbial composition in fecal pellets from C57BL/6N male mice. Mice provided a thiamine regime of 1 mg/kg of low-fat diet for 4 weeks showed marked decreases in fecal community diversity and are characterized by “missing”’ microbes compared to animals provided a standard low-fat thiamine diet (5 mg/kg). Combined with a LC/MS metabolomic analysis these data confirmed changes in the microbiome are coincident with changes of physiological levels of thiamine in the mice. To test the effect of thiamine availability directly on obesity, a separate cohort of C57BL/6N male mice were fed either a low-fat chow (OSD) or an obesogenic soybean oil high fat diet (SO-HFD), with or without supplementation with a thiamine analog (640 mg/kg of diet). Over an 18-week period we found that animals on the SO-HFD with the added thiamine analog gained ~40% less weight compared to animals on the SO-HFD only. Longitudinal sampling of fecal pellets at week 0, 10, 16 and 18 demonstrate major shifts in the microbial composition and diversity over time for animals in all four diet groups. A nested PERMANOVA of Bray-Curtis dissimilarities confirmed the microbiome differences between the SO-HFD and OSD diet (adonis, p = 0.001) and with and without the thiamine analog supplementation (adonis, p = 0.009) at week 16. Measures of microbial diversity show significant increases in diversity for animals consuming the thiamine analog (Kruskall-Wallis, q < 0.05), consistent with the trend observed in the short-term diet trial. Taxonomic classifications for species (ASVs) that significantly increased in these animals are primarily in the Lachnospiraceae family from the Bacillota (Firmicutes) phylum. Together, these data identify major compositional and inferred functional changes to the microbiome in response to the SO-HFD diet as well as thiamine supplementation that may contribute to the observed differences in body weight gain. Funding: The Thiamine Advocacy Foundation. Acknowledgements: UCR Genomics Core. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.