Auricularia auricula polysaccharides alleviate Propionibacterium acnes-induced lung sarcoidosis-like granulomatosis in mice via the gut-lung axis

Abstract

The main aim of this study was to explore the potential of Auricularia auricula polysaccharides (AAP) in treating lung sarcoidosis-like granulomatosis and its regulatory impact on gut microbiota and short-chain fatty acids (SCFAs). A mouse model of the disease was established, and AAP’s therapeutic effect was evaluated using HE staining and PCR. To explore the underlying regulatory mechanisms, 16S rRNA sequencing was used to profile differences in gut microbiota, while untargeted metabolomics and quantitative SCFA analysis were employed to identify key metabolic pathways. Finally, Western blotting of lung tissues was performed to verify the molecular mechanism. Our study revealed that AAP significantly ameliorated pathological changes in lung tissue, decreased mRNA levels of TNF-α, IL-1β, IL-6, and IL-8, modulated gut microbiota composition, regulated the distribution of serum and fecal metabolites to significantly enrich them in the butanoate metabolism pathway, and elevated SCFAs content. These alterations were critical to its protective effects against Propionibacterium acnes (PA)-induced lung sarcoidosis-like granulomatosis. Mechanistically, we found that AAP mediated the enrichment of the beneficial bacteria Bifidobacterium within the gut and enhanced the production of SCFAs, especially butyric acid. This may lead to the suppression of the TLR4/MyD88 inflammatory signaling pathway in the lungs, and thereby effectively combating PA-induced lung sarcoidosis-like granulomatosis inflammation. These findings provided a scientific basis for AAP to alleviate inflammation in experimental lung sarcoidosis-like granulomatosis by modulating gut microbiota and SCFAs production, suggesting that AAP may be a potential drug for the improvement of lung sarcoidosis-like granulomatosis.

Graphical abstract