Probiotics mitigate Helicobacter pylori-induced gastric inflammation and premalignant lesions in INS-GAS mice with the modulation of gastrointestinal microbiota
Probiotics mitigate Helicobacter pylori-induced gastric inflammation and premalignant lesions in INS-GAS mice with the modulation of gastrointestinal microbiota
复制标题
益生菌通过调节胃肠道微生物群减轻 INS-GAS 小鼠幽门螺杆菌诱导的胃部炎症和癌前病变
DOI：
10.1111/hel.12898
复制
发表时间：
2022-05-09
期刊：
影响因子：
4.4
通讯作者：
Lu, Nonghua
中科院分区：
文献类型：
--
作者：
He, Cong;Peng, Chao;Lu, Nonghua
背景胃菌群失调包括幽门螺杆菌感染与胃癌的发生有关。益生菌已被证明可以减轻幽门螺杆菌引起的胃炎，尽管它们在预防癌症方面的作用尚不清楚。因此，我们旨在探讨益生菌对幽门螺杆菌诱导的癌变和胃肠道微生物群改变的影响。方法将雄性INS-GAS小鼠随机分为幽门螺杆菌感染组和未感染组。4周后，在饮用水中给予含唾液乳杆菌和鼠李糖乳杆菌的益生菌组合12周。收集胃标本进行rna测序，采用RT - profiler PCR阵列对差异表达基因进行验证。通过16S rRNA基因测序来评估胃肠道微生物群的变化。结果益生菌可明显减轻幽门螺杆菌引起的胃病理，包括减少炎症浸润和降低癌前病变的发生率。rna测序结果显示，益生菌治疗降低了参与促炎通路的基因的表达，如nf - κ B、IL-17和TNF信号通路。值得注意的是，益生菌并没有抑制幽门螺杆菌的生长，但却极大地重塑了胃和肠道微生物群的结构。益生菌治疗后幽门螺杆菌感染组微生物多样性增加。虽然胃癌相关属乳酸杆菌和葡萄球菌在幽门螺杆菌感染组的胃中丰富，但有益的短链脂肪酸产生细菌，包括拟杆菌，异丙杆菌和Oscellibacter，在益生菌治疗的小鼠中更丰富。此外，益生菌恢复了幽门螺杆菌诱导的肠道中抗炎细菌Faecalibaculum减少。结论益生菌治疗可能通过重塑胃肠道菌群，防止宿主细胞恶性转化，从而预防幽门螺杆菌相关癌变。
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-kappa B, 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.