Bacillus safensis from\nSauerkraut Alleviates Acute Lung Injury Induced by Methicillin-Resistant Staphylococcus aureus through the Regulation of M2\nMacrophage Polarization via Its Metabolite Esculin

Sauerkraut contains various fermentative microorganisms\nthat produce\nactive metabolites, enhancing immunity and resistance to infections.\nHowever, its effects on methicillin-resistant Staphylococcus\naureus (MRSA)-induced acute lung injury (ALI) remain\nunclear. Using RAW264.7 cells and a mouse model, we demonstrated that Bacillus safensis SK14 (BS SK14), an understudied\nfermentative bacterium, has an immunomodulatory effect on MRSA-induced\nALI. BS SK14 significantly reduced the inflammatory responses. Supplementation\nwith live BS SK14 or its culture supernatant increased survival rates,\nreduced lung damage, and attenuated inflammation in ALI model mice.\nLC–MS/MS analysis identified esculin as the key metabolite\nresponsible for these effects. BS SK14 produces esculin via the gut–lung\naxis, inhibiting the TLR2–MyD88–NF-κB pathway,\nreducing Keap1 levels, and activating the Nrf2–ARE pathway.\nThis decreased MRSA-induced M1 polarization and increased M2 polarization,\nenhancing antioxidant and anti-inflammatory activities in mice. Collectively,\nthese results reveal that BS SK14 and its metabolite esculin exert\ntherapeutic effects on MRSA-induced ALI through a multifactorial strategy.