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IL10RA 基因突变的极早发型炎症性肠病患者的肠道微生物群特征及影响

Characteristics of the gut microbiota and the effect of in very early-onset inflammatory bowel disease patients with IL10RA mutations.

作者信息

Xu Xu, Gao Yuanqi, Xiao Yuan, Yu Yi, Huang Jiebin, Su Wen, Li Na, Xu Chundi, Gao Shenshen, Wang Xinqiong

机构信息

Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Tropical Diseases, The Second Affiliated Hospital of Hainan Medical University, Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, China.

出版信息

Front Microbiol. 2024 Dec 2;15:1479779. doi: 10.3389/fmicb.2024.1479779. eCollection 2024.

Abstract

Very early-onset inflammatory bowel disease (VEO-IBD) is a distinct subtype of inflammatory bowel disease (IBD) characterized by onset before the age of 6 years, and patients often exhibit more severe clinical features. Interleukin 10 receptor alpha (IL10RA) is a hotspot mutation in the Chinese population and is associated with a poor prognosis closely linked to the onset of IBD. However, limited knowledge exists regarding how the IL10RA mutation influences the host microbiota and its role in disease development. We employed 16S rRNA sequencing to conduct a comprehensive assessment of microbial changes in different types of IBD, employed database to thoroughly examine the influence of in IBD and to demonstrate a potential positive effect exerted by Bifidobacterium breve M16V (M16V) through a mouse model. The study demonstrated a significant reduction in the abundance and diversity of the gut microbiota among children with IL10RA mutations compared to those with late-onset pediatric IBD and nonmutated VEO-IBD. Furthermore, the analysis identified genera capable of distinguishing between various types of IBD, with the genus emerging as a potential standalone diagnostic indicator and may also be involved in related pathways that influence the progression of IBD, such as the biosynthesis of amino acids and inflammation-related pathways. This study corroborated the efficacy of in alleviating intestinal inflammation. The impact of IL10RA mutations on VEO-IBD may be mediated by alterations in microbes. M16V demonstrates efficacy in alleviating colitis and holds promise as a novel microbial therapy.

摘要

极早发型炎症性肠病(VEO-IBD)是炎症性肠病(IBD)的一种独特亚型,其特征为发病年龄在6岁之前,且患者通常表现出更严重的临床特征。白细胞介素10受体α(IL10RA)是中国人群中的一个热点突变,与IBD发病密切相关的不良预后有关。然而,关于IL10RA突变如何影响宿主微生物群及其在疾病发展中的作用,目前了解有限。我们采用16S rRNA测序对不同类型IBD中的微生物变化进行全面评估,利用数据库深入研究IL10RA在IBD中的影响,并通过小鼠模型证明短双歧杆菌M16V(M16V)发挥的潜在积极作用。该研究表明,与晚发型儿童IBD和未突变的VEO-IBD患儿相比,IL10RA突变患儿的肠道微生物群丰度和多样性显著降低。此外,分析确定了能够区分不同类型IBD的属,其中某属成为一个潜在的独立诊断指标,并且某属也可能参与影响IBD进展的相关途径,如氨基酸生物合成和炎症相关途径。本研究证实了M16V在减轻肠道炎症方面的疗效。IL10RA突变对VEO-IBD的影响可能由微生物变化介导。M16V在减轻结肠炎方面显示出疗效,有望成为一种新型微生物疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77e7/11647010/8dbfc4ed564d/fmicb-15-1479779-g0001.jpg

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