Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Medicine and APC Microbiome Ireland, University College Cork, Cork T12 K8AF, Ireland; School of Microbiology, University College Cork, Cork T12 YT20, Ireland.
Department of Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Cell. 2020 Jan 23;180(2):221-232. doi: 10.1016/j.cell.2019.12.025.
Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.
人类疾病与肠道微生物群落的改变或“失调”密切相关,但这些变化是疾病的原因、后果还是旁观者,在很大程度上仍未得到解决。与人共生的微生物相关(HMA)啮齿动物已成为微生物组科学的基石,可用于解决微生物群落改变与宿主病理学之间的因果关系。在一项系统评价中,我们发现,95%的已发表的关于 HMA 啮齿动物的研究(36/38)报告称,病理表型可转移到受体动物,并且许多研究将这些发现外推到人类疾病中,以做出因果推断。我们认为,这种物种间可转移的病理情况的发生率极高是不合理的,并且夸大了肠道微生物组在人类疾病中的作用。我们主张采取更严格和批判性的方法来推断因果关系,以避免错误的概念,并防止不切实际的期望,这些期望可能会破坏微生物组科学的可信度并延迟其转化。
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