乳酸菌素对幽门螺杆菌感染性胃炎小鼠炎症和肠道菌群的影响

程小英; 詹扬; 周衍安; 张静文; 李颖萌; 刘文君

doi:10.13386/j.issn1002-0306.2023070029

乳酸菌素对幽门螺杆菌感染性胃炎小鼠炎症和肠道菌群的影响

Effects of Lacidophilin on Inflammatory and Intestinal Microflora in Mice with Helicobacter pylori Induced Gastritis

摘要

摘要: 目的：探讨乳酸菌素对幽门螺杆菌（Helicobacter pylori，H. pylori）感染胃炎小鼠炎症和肠道菌群的影响。方法：通过口服H. pylori混悬液制备H. pylori感染小鼠模型。将H. pylori感染成功的小鼠随机分为模型组和乳酸菌素组，进行干预4周。革兰氏染色、Warthin-Starry银染色和H. pylori免疫组化染色验证小鼠胃黏膜H. pylori的定植，HE染色观察小鼠胃黏膜组织病理学改变，免疫组化法测定小鼠胃黏膜iNOS、IL-1β和3-Nitrotyrosine的表达，16S rRNA测序分析肠道菌群结构。结果：造模组小鼠H. pylori定植成功；乳酸菌素能改善H. pylori感染性胃炎小鼠胃组织病理形态；抑制胃黏膜中iNOS、IL-1β和3-Nitrotyrosine的表达。相较于H. pylori感染组，乳酸菌素组小鼠的肠道菌群组成结构具有明显差异。乳酸菌素可通过调节厚壁菌门、拟杆菌门、放线菌门和疣微菌门的组成，增加肠道菌群的多样性。在属水平上，乳酸菌素可促进g_norank_f_Muribaculaceae、阿克曼氏菌属（Akkermansia）和另枝菌属（Alistipes）等产生短链脂肪酸细菌的生长，抑制杜氏杆菌属（Dubosiella）等炎症相关细菌的增殖，改善肠道菌群组成结构。结论：乳酸菌素能够恢复由H. pylori感染破坏的肠道菌群结构，促进有益菌的增殖，降低炎症反应并缓解胃黏膜氧化损伤，对H. pylori感染性胃炎小鼠发挥保护作用。

Abstract: Objective: The aim of this study was to investigate the effect of lacidophilin on inflammation and intestinal microflora in H. pylori-induced gastritis mice. Methods: Established an H. pylori-infected mice model by orally administering an H. pylori suspension. The mice were randomly divided into a model group and a lacidophilin treatment group, which received treatment for four weeks. Gram staining, Warthin-Starry silver staining, and H. pylori immunohistochemical staining were conducted to confirm the colonization of H. pylori in the gastric mucosa of mice. Hematoxylin and eosin (HE) staining was performed to observe any histopathological changes in the gastric mucosa of mice. Immunohistochemistry was carried out to observe the expression of iNOS, IL-1β, and 3-Nitrotyrosine in the gastric mucosa of mice. Additionally, the structure of intestinal microflora was analyzed using 16S rRNA sequencing. Results: The successful establishment of H. pylori-infected mice. Lacidophilin improved the stomach histopathological morphology in mice with H. pylori-induced gastritis and inhibited iNOS, IL-1β, and 3-Nitrotyrosine expression in the gastric mucosa. The composition and structure of the gut microbiota among the lacidophilin group showed noticeable differences in comparison to the H. pylori-infected group. Lacidophilin augmented the diversity of intestinal microflora in H. pylori-infected mice by regulating the abundance of Firmicutes, Actinobacteriota, Bacteroidete, and Verrucomicrobiota. At the genus level, Lacidophilin resulted in significant growth stimulation of beneficial bacteria such as g_norank_f_Muribaculaceae, Akkermansia, and Alistipes, while suppressing the proliferation of inflammation-related bacteria such as Dubosiella, thereby improving the composition and structure of the gut microbiota. Conclusion: Lacidophilin has the potential to rebalance the composition and structure of gut microbiota that has been compromised by H. pylori infection. It may have a protective effect on mice with H. pylori-induced gastritis by promoting the growth of beneficial bacteria, reducing inflammatory reactions, and alleviating oxidative damage to the gastric mucosa.