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.

与人类相关的微生物在人类健康中发挥着至关重要的作用，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微生物的相关研究到建立微生物产物与宿主表型之间因果关系的实验的进展。我们认为，成功揭示表型的努力通常遵循一系列证据，这些证据来自（1）关联研究； (2) 在无菌动物和抗生素治疗的动物和人类中进行观察； （3）粪便微生物移植（FMT）； (4)菌株鉴定；然后 (5) 引发表型的分子。以这个实验“漏斗”为指导，我们探索微生物群如何导致代谢紊乱和高血压、感染和神经系统疾病。我们讨论了使用 FMT 和微生物群启发疗法治疗人类疾病的潜力以及这些方法的局限性。