Probiotics mitigate Helicobacter pylori‐induced gastric inflammation and premalignant lesions in INS‐GAS mice with the modulation of gastrointestinal microbiota

Abstract Background Dysbiosis of gastric microbiota including Helicobacter pylori ( H. pylori ) infection is associated with the development of stomach cancer. Probiotics have been shown to attenuate H. pylori ‐induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on H. pylori ‐induced carcinogenesis and the alterations of gastrointestinal microbiota. Methods Male INS‐GAS mice were randomly allocated to H. pylori ‐infected and non‐infected groups. After 4 weeks, probiotic combination (containing Lactobacillus salivarius and Lactobacillus rhamnosus ) was administered in drinking water for 12 weeks. Stomachs were collected for RNA‐Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota. Results Probiotics significantly alleviate H. pylori ‐induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions. RNA‐Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro‐inflammatory pathways, such as NF‐κB, IL‐17, and TNF signaling pathway. Of note, probiotics did not suppress the growth of H. pylori , but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in H. pylori ‐infected group after probiotics treatment. While gastric cancer‐associated genera Lactobacillus and Staphylococcus were enriched in the stomach of H. pylori ‐infected group, the beneficial short‐chain fatty acids‐producing bacteria, including Bacteroides , Alloprevotella , and Oscellibacter , were more abundant in mice treated with probiotics. Additionally, probiotics restored the H. pylori ‐induced reduction of anti‐inflammatory bacterium Faecalibaculum in the gut. Conclusions Probiotics therapy can protect against H. pylori ‐associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation.