基于胃粘膜菌群探讨膳食纤维对H. pylori易位的影响及机制

Translocation of H. pylori lays a foundation for its pathopoiesis. The mucous barrier plays an important in this process, which can significantly affected by dietary fiber in colon through modulating the gut microbiota. We hypothesized that during the invasion of H. pylori to gastric mucosa, dietary fiber also affects the mucous barrier via modulating gastric microbiota and disturbs the translocation of H. pylori. In this study, to assess the effects of dietary fiber on H. pylori infection, we will first administrate the SPF mice and GF mice with diet containing different dietary fiber content and observe the translocation of H. pylori and the changes of the mucous barrier. Then, we will transplant the gastric microbiota of SPF mice with diet pre-treatment to GF mice, and measure these parameters above to directly evaluate the role of gastric microbiota. Under the guide of high-throughput sequencing, we try to separate some key strains and let them individually colonize in the stomach of GF mice in order to judge their effects. Moreover, clinical samples will also be used to validate these observation. The results of this study will help to deepened our knowledge of the pathopoiesis of H. pylori and explore the potential therapies based on the gastric microbiota.

H. pylori致病的前提在于其发生明显的空间易位，粘液屏障在这一过程起重要作用。膳食纤维能够通过影响结肠菌群显著影响结肠的粘液屏障。本项目提出猜想：在H. pylori侵袭胃粘膜的过程中，膳食纤维会通过影响胃粘膜菌群引起粘液屏障改变，进而影响H. pylori的易位过程。项目将利用不同膳食纤维含量的饮食配方对SPF和GF小鼠行饮食干预，同时结合GF小鼠胃粘膜菌群移植实验和单菌株定植实验，观察膳食纤维对H. pylori易位及粘液屏障的影响，探讨胃粘膜菌群在其中的作用，并尝试利用临床样品在人群层面进行验证。研究结果将有助于加深对H. pylori致病过程的认识，开发基于胃粘膜菌群的防治策略。

H. pylori致病的前提在于其发生明显的空间易位。粘液屏障在致病菌定植、感染过程起重要作用。膳食纤维能够通过调节菌群影响粘液屏障。为此，本项目猜想：在H. pylori侵袭胃粘膜的过程中，膳食纤维能够通过影响胃粘膜菌群引起粘液屏障改变，进而影响H. pylori的易位过程。本项目首先观察、对比了3种不同种类的膳食纤维对胃粘膜菌群和粘液屏障的影响，选定了一种效果较优的膳食纤维开展后续研究；其次，通过对灌胃H. pylori的SPF小鼠、GF小鼠行饮食干预，观察了膳食纤维对H. pylori定植的影响，验证了膳食纤维的作用是否依赖于胃部菌群；最后，检测了HP+/-胃癌患者和健康对照的胃粘膜菌群，分析了HP+人群的胃粘膜菌群特点。研究表明，膳食纤维对胃粘膜菌群和粘液屏障存在显著影响；膳食纤维能够显著抑制H. pylori的定植，且这种抑制作用依赖于胃部菌群；在人群层面，胃部菌群可能同样能在一定程度影响H. pylori的定植、感染。此外，申请人进一步开展了部分延伸工作，为后续菌群易位相关研究做了初步摸索。本项目加深了对H. pylori致病过程的认识，提出了利用膳食纤调节胃粘膜菌群防治H. pylori感染的策略，为探讨菌群易位在疾病发生发展中的重要作用提供了新思路。