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ABSTRACT 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. Access through your institution Buy or subscribe This is a preview of

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* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS GUT MICROBIOTA IN HUMAN METABOLIC HEALTH AND DISEASE

Article 04 September 2020 A CONSENSUS STATEMENT ON ESTABLISHING CAUSALITY, THERAPEUTIC APPLICATIONS AND THE USE OF PRECLINICAL MODELS IN MICROBIOME RESEARCH Article 03 March 2025 CAUSAL

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metabolism. _Mol. Psychiatry_ 21, 786 (2016). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by National Institutes of Health grants R35

GM128618 and R01 DK126855 (A.S.D.). S.N.C. acknowledges an American Heart Association Postdoctoral Fellowship. M.D.M. acknowledges an NSF Graduate Research Fellowship (DGE1745303). Figures

created with BioRender.com. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston,

MA, USA Snehal N. Chaudhari, Megan D. McCurry & A. Sloan Devlin Authors * Snehal N. Chaudhari View author publications You can also search for this author inPubMed Google Scholar * Megan

D. McCurry View author publications You can also search for this author inPubMed Google Scholar * A. Sloan Devlin View author publications You can also search for this author inPubMed 

Google Scholar CORRESPONDING AUTHORS Correspondence to Snehal N. Chaudhari or A. Sloan Devlin. ETHICS DECLARATIONS COMPETING INTERESTS A.S.D. is an ad hoc consultant for Takeda

Pharmaceuticals and Axial Therapeutics. The other authors have declared no competing interests. ADDITIONAL INFORMATION PEER REVIEW INFORMATION _Nature Chemical Biology_ thanks Andrew Gewirtz

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of evidence from correlations to causal molecules in microbiome-linked diseases. _Nat Chem Biol_ 17, 1046–1056 (2021). https://doi.org/10.1038/s41589-021-00861-z Download citation *

Received: 01 September 2020 * Accepted: 16 July 2021 * Published: 22 September 2021 * Issue Date: October 2021 * DOI: https://doi.org/10.1038/s41589-021-00861-z SHARE THIS ARTICLE Anyone you

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