Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nat Chem Biol. 2021 Oct;17(10):1046-1056. doi: 10.1038/s41589-021-00861-z. Epub 2021 Sep 22.
Human-associated microorganisms play a vital role in human health, and microbial imbalance has been linked to a wide range of disease states. In this Review, we explore recent efforts to progress from correlative studies that identify microorganisms associated with human disease to experiments that establish causal relationships between microbial products and host phenotypes. We propose that successful efforts to uncover phenotypes often follow a chain of evidence that proceeds from (1) association studies; to (2) observations in germ-free animals and antibiotic-treated animals and humans; to (3) fecal microbiota transplants (FMTs); to (4) identification of strains; and then (5) molecules that elicit a phenotype. Using this experimental 'funnel' as our guide, we explore how the microbiota contributes to metabolic disorders and hypertension, infections, and neurological conditions. We discuss the potential to use FMTs and microbiota-inspired therapies to treat human disease as well as the limitations of these approaches.
人体相关微生物在人类健康中起着至关重要的作用，微生物失衡与多种疾病状态有关。在这篇综述中，我们探讨了最近从识别与人类疾病相关的微生物的相关性研究进展到建立微生物产物与宿主表型之间因果关系的实验的努力。我们提出，成功揭示表型的努力通常遵循一条证据链，从（1）关联研究；到（2）无菌动物和抗生素处理动物和人类的观察；到（3）粪便微生物群移植（FMT）；到（4）鉴定菌株；然后（5）产生表型的分子。利用这个实验“漏斗”作为我们的指导，我们探讨了微生物组如何导致代谢紊乱和高血压、感染和神经疾病。我们讨论了使用 FMT 和受微生物启发的疗法来治疗人类疾病的潜力，以及这些方法的局限性。
