Multiomics approach reveals the comprehensive interactions between nutrition and children's gut microbiota, and microbial and host metabolomes.

The gut microbiome can modulate nutrient metabolism to produce many metabolites interacting with the host. However, the intricate interactions among dietary intake, the gut microbiome and metabolites, and host metabolites need to be further explored although some studies have been devoted to it. Here, in a cross-sectional studies, 88 children aged 2-12 years were enrolled from northwestern China. The dietary intake data were collected via a designed food frequency questionnaire to calculate plant-based diet indices (PDIs). Stool and plasma samples were collected for metagenomic and broad-targeted metabolomic analysis. Spearman's rank correlation was used to describe the associations between nutrients/PDIs and the gut microbiota and metabolites. PDI was significantly positively associated with Bilophila wadsworthia, Bacteroides thetaiotaomicron, and Alistipes indistinctus, etc., but was obviously negatively correlated with Roseburia intestinalis, Faecalibacterium prausnitzii, etc. However, these species showed no significant associations with either healthy PDI (hPDI) or unhealthy PDI (uPDI). Interestingly, hPDI was significantly positively related to species, including Ruminococcus bicirculans, and was significantly negatively associated with uPDI, and vice versa. The above correlation trends were also observed between PDIs and predicted gut microbial functional pathways, microbial metabolites and the host metabolome. Notably, the significantly related pathways were focused mainly on substances and energy metabolism. PDI was significantly positively associated with the fecal contents of P-aminobenzoate, chenodeoxycholic acid, 4,6-dihydroxyquinoline, quinoline-4,8-diol, etc., but was significantly negatively associated with those of TMAO, FFA, creatine phosphate, etc. In plasma, PDI was significantly positively associated with sarcosine, ornithine, L-histidine, etc., but was distinctly negatively correlated with FFAs, carnitine C2:0, etc. Strikingly, the healthy plant-based diet index (hPDI) is correlated with increased levels of metabolites related to tryptophan metabolism, whereas the unhealthy PDI (uPDI) is linked to increased levels of metabolites associated with tyrosine and sphingolipid metabolism, which are pathways commonly associated with Western diets. Our studies provide reliable data support and a comprehensive understanding of the effects of dietary intake on the gut microbiome and microbial and host metabolites and lay a foundation for further studies of the diet-gut microbiota-microbial metabolites and host metabolism.