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A framework for understanding collective microbiome metabolism

Nature Microbiology volume 9, pages 3097–3109 (2024)Cite this article

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Abstract

Microbiome metabolism underlies numerous vital ecosystem functions. Individual microbiome members often perform partial catabolism of substrates or do not express all of the metabolic functions required for growth. Microbiome members can complement each other by exchanging metabolic intermediates and cellular building blocks to achieve a collective metabolism. We currently lack a mechanistic framework to explain why microbiome members adopt partial metabolism and how metabolic functions are distributed among them. Here we argue that natural selection for proteome efficiency—that is, performing essential metabolic fluxes at a minimal protein investment—explains partial metabolism of microbiome members, which underpins the collective metabolism of microbiomes. Using the carbon cycle as an example, we discuss motifs of collective metabolism, the conditions under which these motifs increase the proteome efficiency of individuals and the metabolic interactions they result in. In summary, we propose a mechanistic framework for how collective metabolic functions emerge from selection on individuals.

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Fig. 1: Proteome-efficient metabolic strategies liberate cellular resources for important physiological traits and underlie major motifs of collective microbiome metabolism.
Fig. 2: Proteome efficiency can be achieved by sharing extracellular metabolism.
Fig. 3: The splitting of catabolic pathways allows higher flux than complete catabolism.
Fig. 4: The impact of carbon entry nodes on anabolite biosynthesis.
Fig. 5: Conflict between autotrophic and heterotrophic metabolism.

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Acknowledgements

We thank R. Naisbit for valuable comments and suggestions; J. Fink for helpful comments on the mathematical models; and A. Flamholz, J.-U. Kreft, S. Kuehn, S. Laxman, M. Scott, A. Spormann, B. Vögeli, members of the NCCR Microbiomes and many interested researchers at conferences for stimulating discussions on the ideas presented here. We also thank the Microbial Systems Ecology group at ETH Zurich and Eawag for creating a fun and supportive work environment. This work was supported by the NCCR Microbiomes (National Centre of Competence in Research, Swiss National Science Foundation; grant 180575 to M.H., O.T.S. and M.A.), Simons Foundation (through the Principles of Microbial Ecosystems (PriME) collaboration; grant 542395 to O.T.S and M.A.), Swiss National Science Foundation (grant 31003A_169978 to M.A.), ETH Zurich and Eawag.

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  1. Matthias Huelsmann

    Present address: PharmaBiome AG, Schlieren, Switzerland

Authors and Affiliations

  1. Department of Environmental Systems Science, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich, Switzerland

    Matthias Huelsmann, Olga T. Schubert & Martin Ackermann

  2. Department of Environmental Microbiology, Swiss Federal Institute of Aquatic Science and Technology (Eawag), Dübendorf, Switzerland

    Matthias Huelsmann, Olga T. Schubert & Martin Ackermann

  3. School of Architecture, Civil and Environmental Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland

    Martin Ackermann

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M.H. and M.A. conceived of the study idea. M.H. developed the conceptual framework, performed the literature research and prepared the figures. All authors wrote the manuscript.

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Huelsmann, M., Schubert, O.T. & Ackermann, M. A framework for understanding collective microbiome metabolism. Nat Microbiol 9, 3097–3109 (2024). https://doi.org/10.1038/s41564-024-01850-3

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