Bifidobacterium pseudocatenulatum AL44 ameliorates Enterococcus faecium-induced lung inflammation through NLRP3 suppression along the gut-lung axis

Abstract

The gut microbiota plays an important role in regulating pulmonary inflammation via the gut-lung axis. In this study, Bifidobacterium pseudocatenulatum AL44, isolated from healthy infant feces, was evaluated in a mouse model of Enterococcus faecium-induced pneumonia. AL44 treatment markedly alleviated lung histopathological injury, oxidative stress, and inflammatory macrophage polarization. These protective effects were associated with modulation of the gut microbiota, characterized by the enrichment of beneficial taxa, enhanced intestinal barrier integrity, and reduced systemic endotoxin and inflammatory cytokine levels. Targeted serum metabolomics revealed significant alterations in amino acid metabolism, particularly within the glycine-serine-threonine-betaine pathway. In vitro studies showed that betaine, a key AL44-associated metabolite, suppressed lipopolysaccharide (LPS)-induced inflammatory response by inhibiting activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway. Collectively, these results imply that AL44 mitigates pulmonary inflammation via modulation of the gut-lung axis, with betaine-mediated suppression of the NLRP3 signaling representing a potential pathway, supporting AL44 as a promising probiotic candidate for the management of pneumonia.