Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation

Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.