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Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota

Nature Reviews Microbiology volume 20, pages 431–443 (2022)Cite this article

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Abstract

The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic–microbiota–host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.

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Fig. 1: Reciprocal interactions between the gut microbiota and xenobiotics.
Fig. 2: Overview of ingested xenobiotics.
Fig. 3: Xenobiotic–gut bacteria interactions.
Fig. 4: An overview of xenobiotic–gut bacteria interactions investigated at the species level.
Fig. 5: Models used to investigate xenobiotic–microbiota–host interactions.

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Acknowledgements

A.E.L. is supported by the Health Protection Research Unit in Chemical and Radiation Threats and Hazards, funded by the National Institute for Health Research (NIHR). K.R.P. and A.E.L. acknowledge funding by UK Medical Research Council (project no. MC_UU_00025/11). M.Z.-K. is supported by the postdoctoral fellowship from the AXA Research Fund. U. Hofer is acknowledged for helpful comments on the manuscript.

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Authors and Affiliations

  1. The Medical Research Council Toxicology Unit, University of Cambridge, Cambridge, UK

    Anna E. Lindell & Kiran R. Patil

  2. European Molecular Biology Laboratory, Heidelberg, Germany

    Maria Zimmermann-Kogadeeva

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  1. Anna E. Lindell
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  2. Maria Zimmermann-Kogadeeva
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  3. Kiran R. Patil
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The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Kiran R. Patil.

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Competing interests

K.R.P. and M. Z.-K. are inventors in patent applications related to the findings and concepts discussed in this review (K.R.P.: US patent application numbers 16966307 and 16966322; M. Z.-K.: US patent application number 17257394). A.E.L. declares no competing interests.

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Nature Reviews Microbiology thanks Filipe Cabreiro, Benoit Chassaing and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Glossary

Organ

The human gut microbiota can be considered as an organ or supra-organ as it is essential for a wide range of functions, from digestion to immune modulation, and is thus fundamental to the host physiology.

Precision medicine

A medicinal approach whereby molecular data is used to make an optimal choice regarding therapeutic intervention in an individualized or in a stratified manner.

Xenobiotics

Compounds foreign to the human body, including drugs, pollutants, toxins, and food additives and contaminants. It has been suggested that, throughout a lifetime, an individual is exposed to around 10,000 to 100,000 different xenobiotics at varying concentrations.

Second liver

The gut microbiota is often also referred to as second liver, as it is involved in metabolic processes and can contribute to biotransformation of xenobiotics.

Alpha diversity

The diversity of microbial species/strains within an individual microbiota or within an individual sample.

Glucose tolerance

The ability of our bodies to deal with a glucose load to keep our blood glucose levels stable.

Macronutrients

Essential components of food used for the growth and/or maintenance of the constituents of the body; the main macronutrients are proteins, carbohydrates and lipids.

Micronutrients

Chemical elements essential for healthy growth and development, albeit required only in trace amounts, such as vitamins or minerals.

Dysbiosis

An imbalance in the composition of the gut microbial strains contributing to a disease state or undesirable symptoms.

Food contact material

Materials that are intended to be in contact with food such as packaging and cooking utensils.

Exo-metabolome

A set of small molecules, or metabolites, that are present extracellularly.

Phages

Phages (or bacteriophages) are viruses that can infect bacteria. Most phages in the gut replicate through incorporation of the phage genome into the bacterial genome, leading to the formation of latent prophages. Stress, such as DNA-damage or xenobiotic exposure, can induce prophages into the virulent stage, leading to viral replication and cell lysis.

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Lindell, A.E., Zimmermann-Kogadeeva, M. & Patil, K.R. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat Rev Microbiol 20, 431–443 (2022). https://doi.org/10.1038/s41579-022-00681-5

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