Akkermania muciniphila ameliorates renal function in a murine model of chronic kidney disease through regulation of the Tryptophan Metabolic Pathway
Background Akkermansia muciniphila (A. muciniphila) improved serum metabolism and renal fibrosis in a mouse model of chronic kidney disease (CKD) via the gut-kidney axis, thereby slowing renal function decline. However, the biological components and underlying metabolic pathways remain unclear. We utilized a mouse model of CKD and administered different biological components of A. muciniphila to identify the constituents responsible for its regulatory effects. Integrated microbiome and metabolomics analyses further elucidated the metabolic mechanisms of renoprotection, providing a theoretical foundation for the development of evidence-based clinical interventions.Methods The CKD mouse model was established by 5/6 nephrectomy, with sham-operated mice (n=7) serving as controls. The 28 CKD mice were randomly assigned to four groups and treated with PBS, A. muciniphila, pasteurized A. muciniphila, and A. muciniphila combined with vancomycin by gavage. Serum and kidney tissue were collected to assess renal function and histopathology for identifying the key biological components of A. muciniphila. Fecal samples were subjected to integrated microbiome and metabolomics analyses to delineate the metabolic pathways involved in renoprotection, while behavioral tests were conducted to evaluate body function.Results Treatment with A. muciniphila, particularly in combination with vancomycin, significantly reduced serum levels of Cr, Bun, Cys-C, and the renal injury marker KIM-1. A. muciniphila monotherapy also induced downward trends in NGAL and the fibrosis markers COL1A1, TIMP-1 and FN. This renoprotection was accompanied by a significant improvement in the physical performance of CKD mice, with the combined intervention yielding more pronounced effects than live or pasteurized bacteria alone. 16S rRNA analysis revealed an improved gut microbiota health index and reduced abundances of Turicibacter, Dubosiella, and norank_f_UCG-010 following A. muciniphila intervention. Metabolomics further showed a strong correlation between A. muciniphila and the tryptophan metabolic pathway.Conclusion Our findings demonstrated that the renoprotective effects of A. muciniphila are mediated by its bioactive components but can be compromised by gut dysbiosis in CKD. Its regulation of tryptophan metabolism improved renal and behavioral outcomes, laying an experimental foundation for further biological mechanism research.