Abstract

Introduction: Little is known about whether the effect of a healthy diet on diabetes mellitus (DM) is modified by the gut microbiome in human. Hypothesis: We hypothesize that the gut microbiome modifies the inverse association between the Mediterranean diet (MedDiet) and risk of DM. Methods: This study included 543 DM cases, 805 with impaired glucose tolerance (IGT) and 394 with normal glucose regulation (NGR) in adults 23-83yrs old from the HCHS/SOL. Fecal samples were profiled using 16s rRNA gene sequencing. We applied QIIME 2 to cluster sequences into OTUs and assign taxonomies, and PICRUSt to predict metagenomic gene functions. Adherence to the MedDiet was evaluated by a MedDiet index using the average of two 24-hr dietary recalls. We applied MaAsLin2 to quantify associations between the MedDiet index and microbial features with adjustment for confounding factors listed in the caption of Fig. 1. Results: MedDiet was associated with phylogenetically diverse, rare, and abundant gut microbes (Fig. 1a). For example, a higher MedDiet index was associated with a higher relative abundance of Faecalibacterium Prausnitzii [FDR-adjusted p (q) =0.002], but a lower relative abundance of Collinsella aerofaciens ( q =0.009). We found that several microbial functions related to plant-derived polysaccharide degradation such as fructuronate reductase ( q =0.02), and short-chain fatty acid fermentation such as butyryl-CoA dehydrogenase ( q =0.002) were enriched in participants with higher MedDiet index. We found that the inverse association between MedDiet and risk of DM was more pronounced in participants with greater abundance of Prevotella copri , but weaker in participants whose gut microbial communities were dominated by Bacteroides ( P interaction =0.02 for IGT/DM vs NGR, Fig. 1b). Conclusions: Adherence to the MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between MedDiet and risk of DM might be modified by gut microbiome composition. 1

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