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Diet-Microbiome Analysis in a Healthy Cohort Reveals Potential Role of Intestinal Microbiota in Metabolism

Trang, K. T.; Gulick, D. A.; Truell, J.; Tian, J.; Bodkhe, R.; Hiseni, P.; Gravdal, K.; Kirubakaran, T. G.; Casen, C.; Singh, R.; Ziegler, T. R.; Reimer, R. A.; Kraft, C. S.

2026-02-20 microbiology
10.64898/2026.02.17.706416 bioRxiv
Show abstract

Both preclinical and clinical studies have revealed the indisputable importance of intestinal bacterial community composition in pathogenesis of various disease states, from obesity to neurodegeneration. Diet remains one of the most important factors shaping human intestinal microbiota composition. In this study, we investigated diet-microbiome interactions in a healthy cohort of 88 participants from Atlanta and Calgary. We examine microbial composition (16S rRNA sequencing) with dietary records using Spearman Correlation tests with Benjamini-Hochberg multiple hypothesis correction to make community-level comparisons between dietary scores and microbial diversity index scores. Predictive models were used for molecular-level comparisons between microbial gene pathways and molecules. Among generalized dietary and microbial indices, we identified a negative association between dietary whole grain consumption and a microbial dysbiosis score. Comparisons between dietary food groups and bacterial family abundance reveal significant associations between dairy consumption and Lactobacillaceae abundance, dietary unsaturated to saturated fatty acid ratio and Clostridia Cluster Family XIII, salt intake and Lachnospiraceae, and consumption of greens and beans and Veillonellaceae. Predictive models of microbial gene pathways and molecules reveal significant positive associations between several dietary fatty acids and microbial short-chain fatty acid fermentation pathways, and between dietary lignans and archaeal methanogenesis pathways. Overall, these associations may inform future explorations on specific dietary interventions to impact the gut microbiome. IMPORTANCEIn this study, we compare dietary records and composition of intestinal microbes in a cohort of 88 participants. We identified associations between dietary consumption of dairy and the presence of dairy-consuming bacteria called Lactobacteriaceae and between consumption of dietary fats and the presence of fat-consuming bacteria called Clostridia. Using predictive analysis, we identify specific fatty acids associated with specific biochemical pathways found in Clostridia that might underlie these associations, in addition to an association between archaeal microbes and dietary consumption of estrogen-binding molecules called lignans, which are commonly found in whole grains and vegetables. Overall, our study generates useful associations between diet and intestinal microbes that can be tested in experiments that may help scientists use diet to control intestinal microbes in order to improve human health.

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