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The individual response to antibiotics and diet — insights into gut microbial resilience and host metabolism

Nature Reviews Endocrinology (2024)Cite this article

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Abstract

Antibiotic use disrupts microbial composition and activity in humans, but whether this disruption in turn affects host metabolic health is unclear. Cohort studies show associations between antibiotic use and an increased risk of developing obesity and type 2 diabetes mellitus. Here, we review available clinical trials and show the disruptive effect of antibiotic use on the gut microbiome in humans, as well as its impact on bile acid metabolism and microbial metabolites such as short-chain fatty acids. Placebo-controlled human studies do not show a consistent effect of antibiotic use on body weight and insulin sensitivity at a population level, but rather an individual-specific or subgroup-specific response. This response to antibiotic use is affected by the resistance and resilience of the gut microbiome, factors that determine the extent of disruption and the speed of recovery afterwards. Nutritional strategies to improve the composition and functionality of the gut microbiome, as well as its recovery after antibiotic use (for instance, with prebiotics), require a personalized approach to increase their efficacy. Improved insights into key factors that influence the individual-specific response to antibiotics and dietary intervention may lead to better efficacy in reversing or preventing antibiotic-induced microbial dysbiosis as well as strategies for preventing cardiometabolic diseases.

Key points

  • Antibiotic use disrupts gut microbial composition and diversity in humans.

  • Observational studies show associations between antibiotic use and an increased risk of weight gain and development of type 2 diabetes mellitus.

  • Short-term placebo-controlled studies do not show a consistent effect of antibiotic-induced disruptions of the gut microbiome on body weight and insulin sensitivity in humans but suggest an individual-specific or subgroup-specific response.

  • The individual-specific or subgroup-specific response to antibiotic use is determined by the resistance and resilience of the gut microbiome, among other factors.

  • Dietary substrates such as prebiotics modulate gut microbial composition and function and might be used to limit the detrimental effects of antibiotic use, but will require a personalized approach to increase their efficacy.

  • More insight into the personalized interaction between the gut microbiome and host metabolism in response to prebiotics and antibiotics might lead to effective prevention of cardiometabolic diseases.

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Fig. 1: Use of antibiotics and prebiotics modulates gut microbial composition and affects similar mechanisms in microbial function, although in opposite directions.
Fig. 2: Antibiotic-induced disruption of the gut microbiome can cause a shift towards an alternative (un)healthy state, depending on resistance, resilience and recovery.

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Authors and Affiliations

  1. Department of Human Biology, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands

    Lars M. M. Vliex & Ellen E. Blaak

  2. Department of Medical Microbiology, Infectious Diseases and Infection Prevention, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands

    John Penders

  3. FrieslandCampina, Amersfoort, The Netherlands

    Arjen Nauta

  4. Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands

    Erwin G. Zoetendal

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  1. Lars M. M. Vliex
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  5. Ellen E. Blaak
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Contributions

E.E.B. and J.P. made a substantial contribution to discussion of content and reviewed/edited the manuscript before submission. L.M.M.V. researched data for the article, made a substantial contribution to discussion of the content and wrote the article. A.N. and E.G.Z. reviewed/edited the manuscript before submission.

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Correspondence to Ellen E. Blaak.

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A.N. is an employee of FrieslandCampina. The other authors declare no competing interests.

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Glossary

Antibiotic

A compound with antibacterial activity. Can be bactericidal (kills bacteria) or bacteriostatic (stops growth).

Human gut microbiome

The ecosystem of bacteria, fungi, archaea and viruses residing in the gastrointestinal tract, especially the intestines and its ‘theatre of activity’.

Microbial dysbiosis

An imbalance in the regular bacterial composition, distribution or activity.

Perturbations

A trigger that can lead to changes in the ecosystem. Can be caused by antibiotic use or a dietary change, among other things.

Prebiotic

A substrate that is selectively utilized by host microorganisms conferring a healthy benefit (defined by the International Association for Probiotics and Prebiotics).

Recovery

The ability of an ecosystem to return to its initial state after a perturbation.

Resilience

The speed at and extent to which the ecosystem returns to its initial state after a perturbation.

Resistance

The ability of an ecosystem to be unaffected by a perturbation and therefore remain in its initial state.

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Vliex, L.M.M., Penders, J., Nauta, A. et al. The individual response to antibiotics and diet — insights into gut microbial resilience and host metabolism. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-00966-0

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