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Tissue-resident bacteria in metabolic diseases: emerging evidence and challenges

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From Nature Metabolism

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Abstract

Although the impact of the gut microbiome on health and disease is well established, there is controversy regarding the presence of microorganisms such as bacteria and their products in organs and tissues. However, recent contamination-aware findings of tissue-resident microbial signatures provide accumulating evidence in support of bacterial translocation in cardiometabolic disease. The latter provides a distinct paradigm for the link between microbial colonizers of mucosal surfaces and host metabolism. In this Perspective, we re-evaluate the concept of tissue-resident bacteria including their role in metabolic low-grade tissue and systemic inflammation. We examine the limitations and challenges associated with studying low bacterial biomass samples and propose experimental and analytical strategies to overcome these issues. Our Perspective aims to encourage further investigation of the mechanisms linking tissue-resident bacteria to host metabolism and their potentially actionable health implications for prevention and treatment.

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Fig. 1: Consensus signatures across tissues and reported studies.
Fig. 2: Sources and mechanisms of bacterial translocation.
Fig. 3: Consequences of bacterial translocation in metabolically active organs.
Fig. 4: Overview of key considerations in microbiome studies involving low bacterial biomass samples.

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Acknowledgements

L.M. was supported by a postdoctoral grant from the Swedish Society for Medical Research (SSMF) and a starting grant from the Swedish Research Council (2023-02839). N.M. was funded by the Novo Nordisk Foundation through an NNF Young Investigator Award, grant NNF22OC0071609 ReFuel. R.C.’s research work was supported by a Walter Benjamin Fellowship grant from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). P.K.’s research work was supported by a grant from the DFG (Projektnummer 209933838 – SFB 1052; B3). We thank T.S. Schmidt (EMBL, Heidelberg, Germany) for rewarding scientific discussions and providing scientific material relating to the tumour microbiome section. We thank D.R. Marquez (@darwid_ilustration) for the contribution to our graphical illustrations.

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  1. These authors contributed equally: Lucas Massier, Rima Chakaroun, Peter Kovacs.

Authors and Affiliations

  1. Department of Medicine (H7), Karolinska Institutet, Stockholm, Sweden

    Lucas Massier

  2. Aarhus University, Department of Biology, Section for Microbiology, Århus, Denmark

    Niculina Musat

  3. Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany

    Michael Stumvoll, Rima Chakaroun & Peter Kovacs

  4. Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

    Valentina Tremaroli & Rima Chakaroun

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L.M., R.C. and P.K. designed the manuscript; L.M. drafted the figures; L.M., R.C., P.K. and N.M. contributed to the literature review; L.M., R.C., P.K. and N.M. wrote the manuscript; M.S. and V.T. edited and discussed the manuscript.

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Correspondence to Rima Chakaroun or Peter Kovacs.

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Massier, L., Musat, N., Stumvoll, M. et al. Tissue-resident bacteria in metabolic diseases: emerging evidence and challenges. Nat Metab (2024). https://doi.org/10.1038/s42255-024-01065-0

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