Host variables confound gut microbiota studies of human disease.
Host variables confound gut microbiota studies of human disease.
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DOI：
10.1038/s41586-020-2881-9
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发表时间：
2020-11
期刊：
影响因子：
64.8
通讯作者：
Belkaid Y
中科院分区：
文献类型：
--
作者：
Vujkovic-Cvijin I;Sklar J;Jiang L;Natarajan L;Knight R;Belkaid Y
检查人类疾病微生物群的研究之间的低一致性是一个普遍的挑战，限制了识别宿主相关微生物与病理学之间因果关系的能力。微生物群组成的个体间广泛异质性加剧了人类微生物群研究中获得假阳性的风险，这可能是由于人类生活方式和生理变量的差异对微生物群产生了不同的影响。在此，我们推断了人类肠道微生物群概况中最大的、普遍的异质性来源，并进一步确定了人类生活方式和生理特征，如果病例和对照之间不均匀匹配，则会混淆微生物群分析，从而产生与人类疾病的虚假微生物关联。令人惊讶的是，我们发现饮酒频率和排便质量是肠道微生物群变异的重要来源，这些变异在健康受试者和患病受试者之间的分布不同，并且可能会混淆研究设计。我们证明，对于许多流行的、高负担的人类疾病，匹配病例和混杂变量的对照可以减少观察到的微生物群差异和虚假关联的发生率。因此，我们提出了一系列推荐的宿主变量，以在人类微生物群研究中捕获，以便匹配比较组，我们预计这将提高解决人类疾病中与疾病相关的肠道微生物群成员的真实性和可重复性。
Low concordance between studies that examine the microbiota in human diseases is a pervasive challenge that limits capacity to identify causal relationships between host-associated microbes and pathology. Risks of obtaining false positives in human microbiota research are exacerbated by wide inter-individual heterogeneity in microbiota composition likely due to population-wide differences in human lifestyle and physiological variables that exert differential impacts on the microbiota. Herein, we infer the greatest, generalized sources of heterogeneity in human gut microbiota profiles and, further, identify human lifestyle and physiological characteristics that, if not evenly matched between cases and controls, confound microbiota analyses to produce spurious microbial associations with human diseases. Surprisingly, we identify alcohol consumption frequency and bowel movement quality as unexpectedly strong sources of gut microbiota variance that differ in distribution between healthy and diseased subjects and can confound study designs. We demonstrate that for numerous prevalent, high-burden human diseases, matching cases and controls for confounding variables reduces observed microbiota differences and incidence of spurious associations. Thus, we present a list of recommended host variables to capture in human microbiota studies for the purpose of matching comparison groups, which we anticipate will increase robustness and reproducibility in resolving true disease-associated gut microbiota members in human disease.
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通讯作者：
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