The beneficial effects of Akkermansia muciniphila and its derivatives on pulmonary fibrosis

Pulmonary fibrosis (PF) is a progressive and debilitating respiratory condition characterized by excessive deposition of extracellular matrix proteins and scarring within the lung parenchyma. Despite extensive research, the pathogenesis of PF remains incompletely understood, and effective therapeutic options are limited. Emerging evidence suggests a potential link between gut microbiota dysbiosis and the development of PF, highlighting the gut-lung axis as a promising therapeutic target. Akkermansia muciniphila (A. muciniphila), a mucin-degrading bacterium residing in the gut mucosal layer, has garnered considerable interest due to its immunomodulatory and anti-inflammatory properties. This study investigates the therapeutic potential of live and pasteurized A. muciniphila, as well as its extracellular vesicles (EVs), in mitigating inflammation and fibrosis in a murine model of carbon tetrachloride (CCl4)-induced PF exacerbated by a high-fat diet (HFD). Male C57BL/6 mice were divided into groups receiving either a normal diet or an HFD, with or without CCl4 administration. The mice were then treated with live or pasteurized A. muciniphila, or its EVs. Lung tissue was analyzed for the expression of inflammatory markers and fibrosis markers using real-time PCR and ELISA. Administration of live and pasteurized A. muciniphila, as well as its EVs, significantly downregulated the expression of inflammatory and fibrosis markers in the lung tissue of CCl4-induced PF mice. Furthermore, these treatments ameliorated the increased production of IL-6 and reduced IL-10 levels observed in the HFD and CCl4-treated groups. These findings suggest that A. muciniphila and its derivatives exert protective effects against pulmonary inflammation and fibrosis, potentially through modulation of the gut-lung axis. The study highlights the therapeutic potential of A. muciniphila and its derivatives as novel interventions for the management of PF, warranting further preclinical and clinical investigations.