Pasteurized Akkermansia muciniphila AKK PROBIO ameliorates inflammation and metabolic disorder in db/db mice with alterations in gut microbiota and hepatic TLR4 / NF ‐ κB and SREBP2 / HMGCR signaling

BACKGROUND: Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), represents a significant global health challenge. Growing evidence indicates that Akkermansia muciniphila, a promising next-generation beneficial microorganism, could help alleviate metabolic disorders. Nevertheless, its strain-specific effects and associated mechanisms require further investigation. Here, we investigated the potential effects of pasteurized A. muciniphila AKK PROBIO in T2DM using db/db mice. RESULTS: Our findings show that pasteurized AKK PROBIO supplementation was associated with lower fasting glucose levels, reduced inflammatory markers, and improved cholesterol balance in db/db mice. Pasteurized AKK PROBIO administration was accompanied by changes in gut microbiota composition, including enrichment of bacterial taxa linked to short-chain fatty acid (SCFA) production, and by increased GLP-1 levels and altered serum metabolites, including 9,9'-di-cis-ζ-carotene and l-arginine. These changes were paralleled by reduced hepatic expression of proteins related to the TLR4/MyD88/IKKα/NF-κB and SREBP2/HMGCR signaling pathways. CONCLUSIONS: Taken together, our findings indicate that pasteurized AKK PROBIO ameliorates metabolic disorder and inflammation in db/db mice, accompanied by changes in gut microbial ecology, serum metabolites, and hepatic inflammatory/lipid metabolic signaling. This study supports pasteurized A. muciniphila AKK PROBIO as a postbiotic for further investigation in metabolic disorders.