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

<i>Helicobacter pylori</i> (<i>H. pylori</i>) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly <i>Lactobacillus</i>, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting <i>H. pylori</i>-induced inflammation are unclear. In our previous study, <i>Lactiplantibacillus plantarum</i> ZJ316 (<i>L. plantarum</i> ZJ316) demonstrated strong anti-inflammatory effects against <i>H. pylori</i> infection <i>in vivo</i>, but its precise mechanisms were not fully understood. Here, we aimed to investigate how <i>L. plantarum</i> ZJ316 inhibits the inflammatory response to <i>H. pylori</i> infection. Our results demonstrated that <i>L. plantarum</i> ZJ316 effectively reduced the expression of pro-inflammatory cytokines in <i>H. pylori</i>-infected AGS cells. Mechanistically, <i>L. plantarum</i> 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 <i>L. plantarum</i> ZJ316 on the NF-κB pathway. In <i>H. pylori</i>-infected mice, oral administration of <i>L. plantarum</i> 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 <i>Prevotella</i> and <i>Desulfovibrio</i>, alongside an increase in <i>Ligilactobacillus</i> and <i>Akkermansia</i>, supporting the protective effects of <i>L. plantarum</i> ZJ316 and correlating with their decreased inflammatory response. In summary, administration of <i>L. plantarum</i> ZJ316 demonstrated robust anti-inflammatory effects against <i>H. pylori</i> infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, <i>L. plantarum</i> ZJ316 holds promise as a novel functional food for protecting the body against <i>H. pylori</i> infection.