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  • Perspective
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How nutrient starvation impacts the gut microbiome

Nature Microbiology volume 10, pages 2663–2672 (2025)Cite this article

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Abstract

Even when the gut is rich in nutrients, microorganisms can experience nutrient deprivation owing to factors such as fluctuations in host feeding patterns, microbial competition and selective nutrient uptake by the host. Nutrient starvation affects microbial survival, microbiome dynamics and intestinal stability, yet remains underexplored. This Perspective explains how nutrient deprivation shapes microbial physiology, ecology and evolution to drive complex interactions both among microbial species and between microorganisms and their host. We discuss host lifestyles that can result in microbial starvation, including diet shifts, fasting and hibernation. We also highlight critical gaps in our understanding of how starvation affects microbial community assembly, stress responses and cross-feeding from lysed cells, with implications for chronic infections and therapeutic strategies. We outline technological developments needed to unravel microbial survival strategies under nutrient deprivation. Understanding how starvation in all its forms shapes the gut ecosystem will be important to ultimately advance microbiome engineering and health interventions.

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Fig. 1: Bacterial strategies to cope with nutrient starvation.
Fig. 2: How bacteria experience nutrient starvation in a host.
Fig. 3: Effect of dietary perturbations on host-associated microbiomes.

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Acknowledgements

We thank members of the Huang Laboratory for helpful discussions. This work was funded by NSF Award EF-2125383 (to K.C.H.) and NIH Award RM1 GM135102 (to K.C.H.). K.C.H. is a Chan Zuckerberg Biohub Investigator.

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  1. Sylvie Estrela

    Present address: Department of Nutrition, Texas A&M University, College Station, TX, USA

Authors and Affiliations

  1. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Sylvie Estrela & Kerwyn Casey Huang

  2. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

    Jonathan Z. Long

  3. Sarafan ChEM-H, Stanford University, Stanford, CA, USA

    Jonathan Z. Long

  4. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA

    Kerwyn Casey Huang

  5. Chan Zuckerberg Biohub, San Francisco, CA, USA

    Kerwyn Casey Huang

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Conceptualization: S.E. and K.C.H. Writing original draft: all authors. Writing, review and editing: all authors. Funding acquisition: K.C.H.

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Correspondence to Sylvie Estrela or Kerwyn Casey Huang.

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Estrela, S., Long, J.Z. & Huang, K.C. How nutrient starvation impacts the gut microbiome. Nat Microbiol 10, 2663–2672 (2025). https://doi.org/10.1038/s41564-025-02139-9

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