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肠道微生物组标志物在 HLA Ⅱ类基因型婴儿亚组中预测普通人群未来的乳糜泻:ABIS 研究。

Gut microbiome markers in subgroups of HLA class II genotyped infants signal future celiac disease in the general population: ABIS study.

机构信息

Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

出版信息

Front Cell Infect Microbiol. 2022 Jul 25;12:920735. doi: 10.3389/fcimb.2022.920735. eCollection 2022.

Abstract

Although gut microbiome dysbiosis has been illustrated in celiac disease (CD), there are disagreements about what constitutes these microbial signatures and the timeline by which they precede diagnosis is largely unknown. The study of high-genetic-risk patients or those already with CD limits our knowledge of dysbiosis that may occur early in life in a generalized population. To explore early gut microbial imbalances correlated with future celiac disease (fCD), we analyzed the stool of 1478 infants aged one year, 26 of whom later acquired CD, with a mean age of diagnosis of 10.96 ± 5.6 years. With a novel iterative control-matching algorithm using the prospective general population cohort, All Babies In Southeast Sweden, we found nine core microbes with prevalence differences and seven differentially abundant bacteria between fCD infants and controls. The differences were validated using 100 separate, iterative permutations of matched controls, which suggests the bacterial signatures are significant in fCD even when accounting for the inherent variability in a general population. This work is the first to our knowledge to demonstrate that gut microbial differences in prevalence and abundance exist in infants aged one year up to 19 years before a diagnosis of CD in a general population.

摘要

尽管在乳糜泻(CD)中已经说明了肠道微生物组失调,但对于构成这些微生物特征的具体内容以及它们在诊断之前出现的时间顺序仍存在争议。对高遗传风险患者或已经患有 CD 的患者的研究限制了我们对可能在一般人群中早期发生的失调的了解。为了探索与未来乳糜泻(fCD)相关的早期肠道微生物失衡,我们分析了 1478 名一岁婴儿的粪便,其中 26 名后来被诊断出患有 CD,平均诊断年龄为 10.96 ± 5.6 岁。使用前瞻性一般人群队列(瑞典东南部所有婴儿)中的新型迭代控制匹配算法,我们发现了 9 种核心微生物,它们在 fCD 婴儿和对照组之间存在流行差异和 7 种丰度差异的细菌。通过对 100 个独立的、迭代的匹配对照组进行验证,这些差异具有统计学意义,这表明即使在考虑一般人群中固有的变异性时,细菌特征在 fCD 中也是显著的。这是我们所知的第一项在一般人群中证明在 CD 诊断前 19 年内,1 岁至 19 岁的婴儿的肠道微生物在流行率和丰度上存在差异的工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/899a/9357981/c4421e11fe7b/fcimb-12-920735-g001.jpg

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