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Microbes and mental health: translating preclinical findings to the clinic

Neuropsychopharmacology volume 49, pages 345–346 (2024)Cite this article

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Almost 20 years ago, the landmark observation was made that germ-free mice, lacking all microbes, showed an exaggerated response to stress and thus ignited neuroscientists to explore the connection between gut microbes and behavior [1]. A robust association between gut microbiota and anxiety-like behavior emerged in animal models [2,3,4]. Based on these key research findings derived from animal studies, clinical studies have finally started to consider the role of the microbiome in psychiatric disorders in humans [5]. Alterations in microbiota diversity and composition have been reported in major depression; however, most studies to date have considered associations between single bacterial taxa and clinical phenotype. Unfortunately, this approach does not consider the community nature of the gut microbiome and therefore ignores how bacteria-host communications influence host physiology. These host communications are critical because we know that it is not simply a single bacteria taxa that change host physiology—rather, it is the interplay of all of the bacteria within the host.

Public interest in the role of the microbiome in mental health continues to grow and it is regularly featured in the media. Microbiome research has already delivered positive clinical impacts in medical areas, including cancer immunotherapy and metabolic disorders. The time is now to leverage the potential of microbiome-related approaches to help us understand the individual biological differences in clinical populations. In this landscape, our data-driven approach has identified a microbiota-biomarker and a potential microbial-host mechanism underlying anxiety in the context of MDD. This is a critical step toward understanding the association between the microbiome and MDD, and how a community-driven approach may facilitate effective precision medicine to improve clinical outcomes.

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Fig. 1: Original findings from germ-free mice led to the modern-day consideration of the impact of the microbiome on mental health outcomes in humans.

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Acknowledgements

The authors would like to thank Jane A. Foster for her contributions to the research highlighted above and for her assistance with the creation of this document.

Funding

The following funding information is for the manuscript from the authors highlighted above ([6]). The Dallas 2K (D2K) study was funded by the Hersh Foundation and the Rose Foundation. The Resilience in Adolescent Development (RAD) study was funded in part by the W.W. Caruth Jr. Foundation, the Elizabeth Jordan Harris Foundation, the Rose Foundation, and the Hersh Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the various funding organizations. In addition, this work was funded in part by the Center for Depression Research and Clinical Care (PI: Madhukar H. Trivedi) and by the Ontario Brain Institute (PI: Sidney Kennedy).

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Authors and Affiliations

  1. Center for Depression Research and Clinical Care, Peter O’Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Cherise R. Chin Fatt & Madhukar H. Trivedi

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  1. Cherise R. Chin Fatt
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  2. Madhukar H. Trivedi
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CRCF and MHT drafted, edited, and approved the manuscript.

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Correspondence to Madhukar H. Trivedi.

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Competing interests

CRCF has no conflicts to disclose. MHT has served as a consultant or advisor for Acadia Pharmaceuticals, Inc., Akili Interactive, Alkermes, Inc. (Pub Steering Comm-ALKS5461), Allergan Sales LLC, Alto Neuroscience, Inc., Applied Clinical Intelligence, LLC (ACI), Axome Therapeutics, Boehringer Ingelheim, Engage Health Media, Gh Research, GreenLight VitalSign6, Inc., Heading Health, Inc., Health Care Global Village, Janssen – Cilag.SA, Janssen Research and Development, LLC (Adv Committee Esketamine), Janssen Research and Development, LLC (panel for study design for MDD relapse), Janssen – ORBIT, Legion Health, Jazz Pharmaceuticals, Lundbeck Research U.S.A, Medscape, LLC, Merck Sharp & Dohme Corp., Mind Medicine (MindMed) Inc., Myriad Neuroscience, Neurocrine Biosciences Inc, Navitor, Pharmaceuticals, Inc., Noema Pharma AG, Orexo US Inc., Otsuka Pharmaceutical Development & Commercialization, Inc. (PsychU, MDD Section Advisor), Otsuka America Pharmaceutical, Inc. (MDD expert), Pax Neuroscience, Perception Neuroscience Holdings, Inc., Pharmerit International, LP, Policy Analysis Inc., Rexahn Pharmaceuticals, Inc., Sage Therapeutics, Signant Health, SK Life Science, Inc., Takeda Development Center Americas, Inc., The Baldwin Group, Inc., and Titan Pharmaceuticals, Inc. MHT also received editorial compensation from Oxford University Press.

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Chin Fatt, C.R., Trivedi, M.H. Microbes and mental health: translating preclinical findings to the clinic. Neuropsychopharmacol. 49, 345–346 (2024). https://doi.org/10.1038/s41386-023-01695-0

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