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Moving from genome-scale to community-scale metabolic models for the human gut microbiome

Nature Microbiology volume 10, pages 1055–1066 (2025)Cite this article

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Abstract

Metabolic models of individual microorganisms or small microbial consortia have become standard research tools in the bioengineering and systems biology fields. However, extending metabolic modelling to diverse microbial communities, such as those in the human gut, remains a practical challenge from both modelling and experimental validation perspectives. In complex communities, metabolic models accounting for community dynamics, or those that consider multiple objectives, may provide optimal predictions over simpler steady-state models, but require a much higher computational cost. Here we describe some of the strengths and limitations of microbial community-scale metabolic models and argue for a robust validation framework for developing personalized, mechanistic and accurate predictions of microbial community metabolic behaviours across environmental contexts. Ultimately, quantitatively accurate microbial community-scale metabolic models could aid in the design and testing of personalized prebiotic, probiotic and dietary interventions that optimize for translationally relevant outcomes.

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Fig. 1: Community-scale metabolic modelling.
Fig. 2: Example of community-scale metabolic modelling for the human gut microbiome.

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Acknowledgements

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award R01DK133468 (to S.M.G.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. C.D. acknowledges funding from the Austrian Science Fund, Cluster of Excellence COE7. The funders had no role in designing, carrying out or interpreting the work presented in this manuscript.

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Authors and Affiliations

  1. Institute for Systems Biology, Seattle, WA, USA

    Nick Quinn-Bohmann, Alex V. Carr, Christian Diener & Sean M. Gibbons

  2. Molecular Engineering Graduate Program, University of Washington, Seattle, WA, USA

    Nick Quinn-Bohmann, Alex V. Carr & Sean M. Gibbons

  3. Diagnostic and Research Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria

    Christian Diener

  4. Department of Bioengineering, University of Washington, Seattle, WA, USA

    Sean M. Gibbons

  5. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Sean M. Gibbons

  6. eScience Institute, University of Washington, Seattle, WA, USA

    Sean M. Gibbons

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Correspondence to Christian Diener or Sean M. Gibbons.

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Quinn-Bohmann, N., Carr, A.V., Diener, C. et al. Moving from genome-scale to community-scale metabolic models for the human gut microbiome. Nat Microbiol 10, 1055–1066 (2025). https://doi.org/10.1038/s41564-025-01972-2

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