Fecal Microbiome and Serum Metabolome Profiles of the Ovarian Failure Mouse Model

Ovarian dysfunction is closely associated with reproductive aging and systemic metabolic disturbances; however, the underlying microbial and metabolic mechanisms remain unclear. In this study, we analyzed fecal microbiome and serum metabolome profiles in young (7-week-old) and aged (12-month-old) female C57BL/6J mice using shotgun metagenomic sequencing and untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry. Microbial and metabolic data were processed using QIIME2, HUMAnN, and MetaboAnalyst 5.0. Differential taxa and metabolites were identified using DESeq2 and linear discriminant analysis effect size (LEfSe), and their associations were evaluated using Spearman's correlation analysis. Our results showed that aged mice exhibited significant alterations in gut microbiota composition, including a decreased abundance of Firmicutes and an increased abundance of Bacteroidetes, along with enrichment of the genera Alistipes and Akkermansia. Serum metabolomic profiling identified 246 differential metabolites, primarily involved in amino acid and energy metabolism pathways. Integrated analysis revealed that tryptophan metabolism represents a key pathway linking microbial dysbiosis with systemic metabolic alterations. Notably, enriched microbial taxa, including Akkermansia muciniphila and species within the genus Alistipes, were strongly correlated with tryptophan-related metabolites. These findings indicate that ovarian failure is associated with coordinated alterations in the gut microbiome and serum metabolome, converging on tryptophan metabolism. This study provides new insights into host-microbiome-metabolite interactions in ovarian failure and highlights potential microbial and metabolic targets for therapeutic intervention.