BACKGROUND: The gut microbiome plays a critical role in human health and disease. Different dietary backgrounds play an important role in the uniqueness and diversity of the gut microbiota in different individuals, which promotes heterogeneity in disease phenotypes and treatment responses. Here, we explored how diet affects the composition and function of the native gut microbiome of model mice, based on the shotgun metagenomic and metabolomic, by analyzing the gut microbiome of C57B/6J mice in different dietary backgrounds. RESULTS: The gut microbiomes of mice receiving different diets consistently exhibit distinct compositions across bacterial species, strains, fungi and phages. This implies that native microbial communities cannot 'homogenize' rapidly becaise of priority effects and unchanging diets. Notably, hotspot bacteria such as Limosilactobacillus reuteri, Parabacteroides distasonis and Akkermansia muciniphila were significantly different among the groups. These species harbor diverse adaptive mutations, reflecting genomic evolutionary diversity. The functional profiles of the gut microbiota also exhibit selective differences, involving the capacity for carbohydrate, branched-chain amino acid and fatty acid synthesis, as well as virulence factors, carbohydrate-active enzymes and antibiotic resistance. Furthermore, the differences in the gut microbiota also propagate to the host's serum, where structural and specific metabolite differences were observed. Metabolites that directly impact host health, such as d-glucosamine 6-phosphate and testolic acid, also show significant differences between the different dietary groups. CONCLUSION: Our findings underscore the profound influence of different dietary the composition and functionality of the gut microbiome, offering valuable insights into optimizing health outcomes through personalized nutritional interventions. © 2024 Society of Chemical Industry.