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肠道微生物组失调与炎症性肠病。

Gut microbiome dysbiosis in inflammatory bowel disease.

机构信息

Molecular Genetics Laboratory, Infection and Immunology Division, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, Faridabad, India.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Prog Mol Biol Transl Sci. 2022;192(1):179-204. doi: 10.1016/bs.pmbts.2022.09.003. Epub 2022 Oct 3.


DOI:10.1016/bs.pmbts.2022.09.003
PMID:36280319
Abstract

Inflammatory bowel disease (IBD) is a complex multi-factorial chronic relapsing disease of the digestive tract where dysbiosis of autochthonous intestinal microbiota, environmental factors and host genetics are implicated in the disease development, severity, course and treatment outcomes. The two clinically well-defined forms of IBD are Crohn's disease (CD) and ulcerative colitis (UC). The CD affects the local immune response of the entire gastrointestinal tract whereas the inflammation in UC is mainly restricted to the colonic mucosa. Prolong progressive inflammation due to CD and UC often lead to colonic cancer. In healthy individuals, the enormous taxonomic diversity and functional potency of gut microbiota including members from the bacterial and fungal microbiota tune the host immunity and keep the gastric environment beneficial and protective. However, expansion of pathobionts, autochthonous microbes with the potency of pathogenicity in dysbiotic condition, in the gastrointestinal tract and subsequently enriched inflammatory microbial products in the gastrointestinal milieu attract different immune cells and activate aberrant host immune response which leads to excessive production and secretion of different cytokines that damage the colonic epithelial cells and manifest chronic inflammatory digestive disease. In the current chapter, we provided our updated understanding about the different bacterial and fungal pathobionts, their genomic and metabolic signatures, and geo-specific diversity of gut microbes linked with IBD across the globe at the molecular resolution. An improved understanding of IBD and the factors associated with the disease will be a boost for therapeutic development and disease management.

摘要

炎症性肠病(IBD)是一种复杂的多因素慢性复发性消化道疾病,其发病机制涉及肠道固有微生物菌群失调、环境因素和宿主遗传因素,这些因素影响疾病的发展、严重程度、病程和治疗效果。临床上明确的两种 IBD 形式是克罗恩病(CD)和溃疡性结肠炎(UC)。CD 影响整个胃肠道的局部免疫反应,而 UC 的炎症主要局限于结肠黏膜。由于 CD 和 UC 的长期进行性炎症,常导致结肠癌。在健康个体中,肠道微生物菌群的巨大分类多样性和功能潜力,包括细菌和真菌菌群的成员,调节宿主免疫,保持胃环境有益和保护。然而,胃肠道中条件致病菌(具有致病性潜力的本土微生物)的扩张,以及随后在胃肠道环境中丰富的炎症性微生物产物,吸引不同的免疫细胞,并激活异常的宿主免疫反应,导致不同细胞因子的过度产生和分泌,从而损伤结肠上皮细胞,表现出慢性炎症性消化道疾病。在本章中,我们提供了关于不同细菌和真菌条件致病菌及其基因组和代谢特征的最新认识,以及与全球 IBD 相关的特定地理环境下肠道微生物的多样性。对 IBD 及其相关因素的认识的提高将促进治疗方法的发展和疾病的管理。

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