Comprehensive multi omics explore the microbial function in metabolic pathway flow during altered diet.

High-protein diet (HPD) and high-fiber diet (HFiD) are two common types of diet, and the transition from HPD to HFiD frequently happens in people who perform diet control. Gut microbiota provide a bridge between diet and health. However, most of the research left out the metabolic landscape change and gut microbial influence under this kind of altered diet. Here, we examined gut microbiome and metabolites change using multi-omics (16S rRNA gene sequencing, shotgun metagenomics, LC-MS/MS metabolomics), and machine-learning methods were introduced to capture the response of gut microbiota to altered diet and associate the variable metabolites and microbial factors. The results suggest that the conversion from HPD to HFiD improves the gut microbial diversity and promotes the pathways of tryptophan, galactose, fructose, and mannose metabolism, which are associated with different gut microbiota and special metabolites. Among them, Faecalibacterium rodentium and Akkermansia muciniphila indicate potential roles in the multi-metabolism. Although these findings are exploratory and hypothesis-generating, they provide a foundation for future mechanistic investigations and emphasize the importance of diverse diets.