Associations of dietary diversity with the gut microbiome, fecal metabolites, and host metabolism: results from 2 prospective Chinese cohorts

Dietary diversity is essential for human health. The gut ecosystem provides a potential link between dietary diversity, host metabolism, and health, yet this mechanism is poorly understood.Here, we aimed to investigate the relation between dietary diversity and the gut environment as well as host metabolism from a multiomics perspective.Two independent longitudinal Chinese cohorts (a discovery and a validation cohort) were included in the present study. Dietary diversity was evaluated with FFQs. In the discovery cohort (n = 1916), we performed shotgun metagenomic and 16S ribosomal ribonucleic acid (rRNA) sequencing to profile the gut microbiome. We used targeted metabolomics to quantify fecal and serum metabolites. The associations between dietary diversity and the microbial composition were replicated in the validation cohort (n = 1320).Dietary diversity was positively associated with α diversity of the gut microbiota. We identified dietary diversity-related gut environment features, including the microbial structure (β diversity), 68 microbial genera, 18 microbial species, 8 functional pathways, and 13 fecal metabolites. We further found 332 associations of dietary diversity and related gut environment features with circulating metabolites. Both the dietary diversity and diversity-related features were inversely correlated with 4 circulating secondary bile acids. Moreover, 16 mediation associations were observed among dietary diversity, diversity-related features, and the 4 secondary bile acids.These results suggest that high dietary diversity is associated with the gut microbial environment. The identified key microbes and metabolites may serve as hypotheses to test for preventing metabolic diseases.