Probiotic <i>Akkermansia muciniphila</i> alleviates acute kidney injury by protecting the intestinal barrier and modulating gut microbiota and metabolites

Acute kidney injury (AKI) is a critical condition with limited effective therapies. Akkermansia muciniphila ( A. muciniphila) is a probiotic with multiple beneficial effects, including the regulation of epithelial cell tight junctions. Since renal pathophysiology is associated with gut barrier integrity, we hypothesized that A. muciniphila may have preventive effects on AKI. We established a lipopolysaccharide (LPS)-induced AKI mouse model to evaluate the effects of A. muciniphila. Our findings showed that pretreatment with A. muciniphila significantly attenuated kidney injury, as evidenced by reduced serum creatinine and urea nitrogen levels, alongside decreased tubular necrosis and apoptosis. A. muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome. A. muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes. At the genus level, Prevotella, Faecalibaculum, Moraxella, and Lactobacillus were more abundant in A. muciniphila-pretreated mice. Metabolomic analysis revealed that A. muciniphila altered the gut metabolome, with changes involving pathways such as tyrosine metabolism, alanine/aspartate/glutamate homeostasis, cancer-related carbon flux, and GABAergic synaptic signaling. In conclusion, our findings indicate that A. muciniphila exerts renoprotective effects by modulating the gut-kidney axis, thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.