Probiotic Akkermansia muciniphila alleviates acute kidney injury by protecting the intestinal barrier and modulating gut microbiota and metabolites.

Abstract

Acute kidney injury (AKI) is a critical condition with limited effective therapies. Akkermansia muciniphila ( A. muciniphila) is a probiotic with multiple beneficial effects, including epithelial cell tight junctions regulation. Since renal pathophysiology is associated with gut barrier integrity, we hypothesized that A. muciniphila may have potential 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 diminished tubular necrosis and apoptosis. A. muciniphila preserved the intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome. A. muciniphila induced notably an increase in the relative abundance of phylum Proteobacteria while a decrease of 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 affecting modulation of pathways, including tyrosine metabolism, alanine/aspartate/glutamate homeostasis, cancer-related carbon flux, and GABAergic synaptic signaling. In conclusion, our findings demonstrate A. muciniphila's renoprotective effects through gut-kidney axis modulation, laying the foundation for subsequent studies to verify the connection between gut microbiota and AKI.