Lactiplantibacillus plantarum LP15-1 regulates intestinal innate immunity via suppressing the NF-κB pathway to modulate M cell differentiation.

Lactobacillus species are increasingly recognized for their essential role in mitigating intestinal inflammation, yet their precise mechanisms of action are not fully understood. This study aimed to investigate the protective effects and underlying mechanisms of a specific probiotic strain, Lactiplantibacillus plantarum LP15-1, in a model of lipopolysaccharide (LPS)-induced intestinal inflammation. Dietary supplementation with LP15-1 alleviated intestinal inflammation and was associated with alterations in the experimental model. Mechanistically, LP15-1 reduced the concentrations of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-1 beta (IL-1β), in both serum and ileal tissue. This anti-inflammatory effect was mediated through the inhibition of key signaling proteins in the canonical and non-canonical nuclear factor kappa-B (NF-κB) pathways. Additionally, LP15-1 suppressed intestinal microfold cell (M cell) differentiation and enhanced relevant immune cell populations. Notably, LP15-1 intervention significantly altered the beta diversity of the gut microbiota, inhibited the over-proliferation of Proteobacteria, restored the abundance of Bacteroidota as well as beneficial genera such as Alloprevotella and Lactobacillus, and reduced the abundance of opportunistic pathogens including Streptococcus and Escherichia-Shigella. Collectively, these findings reveal that LP15-1 ameliorates LPS-induced intestinal inflammation by modulating the canonical and non-canonical NF-κB pathways and suppressing intestinal M cell differentiation, while also being associated with favorable shifts in gut microbiota composition. However, the causal relationship between microbiota changes and the anti-inflammatory effects requires further investigation. The study provides new insights into probiotic-mediated intestinal immunoregulation and supports the potential of LP15-1 as a therapeutic candidate for intestinal inflammatory diseases.