Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.

Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.
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炎症性肠病的微生物组变异排名:一项大型纵向洲际研究。

DOI:
10.1136/gutjnl-2020-321106
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发表时间:
2021-03
期刊:
Gut
影响因子:
24.5
通讯作者:
Claesson MJ
Claesson MJ
中科院分区:
医学1区
文献类型:
--
作者:
Clooney AG;Eckenberger J;Laserna-Mendieta E;Sexton KA;Bernstein MT;Vagianos K;Sargent M;Ryan FJ;Moran C;Sheehan D;Sleator RD;Targownik LE;Bernstein CN;Shanahan F;Claesson MJ

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微生物群与炎症性肠病(IBD)的发病机制有关,但不同生活方式和环境因素对肠道微生物群组成变异的相对影响尚不清楚。在这里,我们对克罗恩病 (CD;n = 303)、溃疡性结肠炎 (UC;n = 228) 和对照 (n = 161) 患者的疾病活动、药物、饮食和粪便微生物群组成的地理位置(16S rRNA 基因测序)的大小效应进行排名,并进行纵向跟踪(在三个时间点,间隔 16 周)。与对照组相比,CD 和 UC 的微生物群多样性降低,但变异性增加。疾病(尤其是 CD)与对照之间的显着组成差异是显而易见的。纵向分析显示 IBD 患者的时间微生物群稳定性降低,特别是在疾病活动度发生变化的患者中。当对连续时间点进行建模时,机器学习将疾病与对照、活动疾病与非活动疾病分开。地理位置占微生物群差异的大部分,其次是 CD 的存在或不存在,其次是手术切除史、饮酒和 UC 诊断、药物和饮食,其中大多数 (90.3%) 的组成差异是随机或无法解释的。精准医学的流行概念和对微生物群的任何治疗操作的合理设计不仅必须应对宿主反应的异质性,而且还要应对生活方式的巨大差异以及许多尚未解释的差异。
The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn’s disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.
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发表时间: 2013-01-07
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DOI: 10.1126/science.aad3503
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