Lacticaseibacillus rhamnosus CP-1 mitigates LPS-induced acute lung injury in mice via TLR/NF-κB pathway and gut microbiota modulation

Abstract

Acute lung injury (ALI) is a severe clinical condition often caused by excessive inflammation, frequently associated with bacterial infections and sepsis. This study investigated the protective effects and underlying mechanisms of the probiotic Lacticaseibacillus rhamnosus (L. rhamnosus) CP-1 and its cell-free supernatant (CFS) on lipopolysaccharide (LPS)-induced ALI mouse model. The findings revealed that CP-1 and CFS significantly ameliorate the pulmonary pathological changes caused by LPS and suppress pulmonary inflammation, evidenced by the reduction of pro-inflammatory cytokines levels, decreased myeloperoxidase (MPO) activity, and inhibition of inhibitor kappa B alpha (IκBα) and p65 protein phosphorylation. Moreover, after treatment with CP-1 and CFS, the transcriptional activity of the toll-like receptor/nuclear factor kappa B (TLR/NF-κB) signaling pathway was altered, leading to significant regulation of the expression of a series of genes related to ALI, which may serve as molecular targets for ALI therapy. Concurrently, CP-1 and CFS increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Bacteroides acidifaciens, Bifidobacterium pseudolongum, and Faecalibaculum rodentium. These changes in gut microbiota composition were correlated with reduced inflammation, suggesting that SCFA-producing bacteria may play a role in mediating the anti-inflammatory effects. Faecalibaculum rodentium, Bacteroides faecis, Parabacteroides goldstein, Lactobacillus, Odoribacter, and Alloprevotella may be beneficial microbial markers for mitigating ALI. In conclusion, the results demonstrated that L. rhamnosus CP-1 and its CFS pretreatment are protective against LPS-induced ALI by suppressing lung inflammation mediated by TLR/NF-κB pathway and reshaping gut microbiota. The limitations of this study include the lack of in-depth analysis of SCFAs and the insufficient exploration of the dose-dependent effects of L. rhamnosus CP-1. Future research will focus on elucidating the mechanisms of SCFAs and investigating a broader range of L. rhamnosus CP-1 doses to clarify its dose-dependent effects.