Bacillus-based probiotics ameliorate bleomycin-induced pulmonary fibrosis in rats: coupling intestinal barrier reinforcement to the modulation of M2 macrophage polarization/TGF-β/p38MAPK and inflammasome-driven pyroptosis.

Pulmonary fibrosis (PF) is a chronic, progressive lung disorder with an 87.5% mortality rate recorded in aged patients. Emerging evidence bridges gut dysbiosis to PF pathogenesis. The consumption of a Bacillus-based probiotic exhibited immunomodulatory and anti-inflammatory effects by alleviating gut dysbiosis and restoring gut microbiome composition, positioning it as a promising therapeutic strategy for gut-organ axis disorders. The present study investigated the therapeutic effects of Bacillus-based probiotics in a rat model of PF by targeting the gut-lung axis. Rats were randomly assigned to five groups: Group I (the normal control group) and Group II received a single intratracheal instillation of bleomycin (BLM) (5 mg/kg). All treated groups received BLM and commenced treatment fourteen days later. Group III: received B. clausii. Group IV: received B. coagulans. Group V: received a combination of both strains. In vitro and in vivo analyses showed that the probiotic strains exhibited gut survivability, colonization associated with restoration of intestinal barrier integrity, and an SCFA profile. The dual therapy exerted a notable immunomodulatory effect by suppressing pulmonary M2 macrophage polarization (CD206 and Arg1), inhibiting the TGF-β/p38MAPK-JNK/NF-κB signaling cascade, mitigating inflammatory and fibrotic responses, and diminishing NLRP3/Caspase-1/IL-1β/GSDMD-N-mediated pyroptosis, thereby disrupting the vicious cycle of inflammation and fibrogenesis. Interplay with the Nrf2 axis activates antioxidant defense. This study resolves this knowledge gap by investigating the therapeutic potential of Bacillus-based probiotics to alleviate PF by modulating the gut-lung axis, offering an innovative platform for the treatment of PF that extends beyond current Lactobacillus-focused research.