肠道真菌在粪菌移植治疗炎症性肠病过程中的作用机制研究

Inflammatory bowel disease (IBD) is a complex group of recurrent inflammatory disorders affecting the gastrointestinal tract and increase the economic burden of family and society. Its incidence is increasing in China in recent years. Many studies have found that the occurrence and development of IBD were closely related to the dysbiosis of gut microbiota. Fecal microbiota transplantation (FMT), as a therapy that can rebuild gut microbiota, has become an alternative treatment of IBD and an appropriate clinical model to study the pathogenesis of IBD. Studies have shown that the bacterial and viral composition in fecal can significantly influence the success of FMT in the treatment of IBD, but the role of gut mycobiome (fungi) has not been reported. As an important group of gut microbiota, gut fungi are also closely related to human health. Therefore, we should fully consider the role of gut fungi when studying the relationship between gut microbiota and IBD. In this study, the gut fungi in fecal and immune factors and metabolites in serum from IBD patients treated with FMT and healthy donors will be investigated. We set to elucidate the role and mechanisms of gut fungi, and their interactions with gut bacteria in the treatment of IBD by FMT. This project will provide important theoretical and practical guidance for the human health and provide more understanding on gut fungi.

炎症性肠病(Inflammatory bowel disease, IBD)是一类慢性，自发免疫性的肠道炎症性疾病，近年来在我国发病率不断升高。IBD的发生发展和肠道菌群紊乱关系很大，而粪菌移植(Fecal microbiota transplantation，FMT)由于可以重建肠道菌群稳态，成为治疗IBD的可选方案。粪菌中的细菌和病毒组均可影响FMT治疗IBD的效果，但肠道真菌的作用目前还没有报道。肠道真菌作为肠道菌群的重要类群，同样与人类健康密不可分。因此，在肠道菌群与IBD关系的研究中，应该充分考虑肠道真菌的影响。本课题拟利用FMT治疗IBD患者队列，对比研究IBD患者与健康供体人群、FMT治疗成功与失败的IBD患者治疗前后的粪便中肠道菌群和血清中免疫因子和代谢产物的差异，阐明肠道真菌及其与细菌互作在FMT治疗IBD过程中的作用机制，为通过调控肠道真菌保障人类健康提供实践指导。

肠道菌群的变化及失衡与宿主息息相关，能够影响宿主的健康和疾病状态。炎症性肠病(Inflammatory bowel disease, IBD)是一类慢性，自发免疫性的肠道炎症性疾病，近年来在我国发病率不断升高，IBD的发生发展和肠道菌群紊乱关系很大，而粪菌移植(Fecal microbiota transplantation，FMT)由于可以重建肠道菌群稳态，成为治疗IBD的可选方案。肠道真菌作为肠道菌群的重要类群，其多样性与群落结构的变化也可以影响宿主疾病的发生与发展。本项目中，我们首先建立了肠道真菌的富集方法和基于三代测序的肠道真菌菌群鉴定方法和分析流程，提高了人粪便等真菌含量稀少样本的真菌DNA比例和真菌分类鉴定的精确度；基于已建立的方法，对比研究健康人群和IBD患者粪便中肠道菌群的差异发现，健康人群和IBD患者在肠道细菌和肠道真菌的alpha多样性和beta多样性均存在差异，并通过LEFSE分析获得了可能影响IBD发生发展的肠道真菌和肠道细菌谱，并揭示了同种肠道微生物在健康人群和IBD患者中基因组结构和执行的功能不同；通过网络分析，阐明了肠道细菌和肠道真菌的互作模式，证明了肠道真菌处在互作网络模块中的核心位置。这些结果在未来可以极大的促进肠道真菌组在人类健康领域的研究和发展。