Identification of medication–microbiome interactions that affect gut infection

Aman Kumar, Ruizheng Sun, Bettina Habib, Tong Deng, Natasha A. Bencivenga-Barry, Noah W. Palm, Ivaylo I. Ivanov, Robyn Tamblyn and Andrew L. Goodman ()
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Aman Kumar: Yale University School of Medicine
Ruizheng Sun: Yale University School of Medicine
Bettina Habib: McGill University
Tong Deng: Yale School of Medicine
Natasha A. Bencivenga-Barry: Yale University School of Medicine
Noah W. Palm: Yale School of Medicine
Ivaylo I. Ivanov: Columbia University
Robyn Tamblyn: McGill University
Andrew L. Goodman: Yale University School of Medicine

Nature, 2025, vol. 644, issue 8076, 506-515

Abstract: Abstract Most people in the USA manage their health by taking at least one prescription drug, and drugs classified as non-antibiotics can adversely affect the gut microbiome and disrupt intestinal homeostasis1,2. Here we identify medications that are associated with an increased risk of gastrointestinal infections across a population cohort of more than one million individuals monitored over 15 years. Notably, the cardiac glycoside digoxin and other drugs identified in this epidemiological study are sufficient to alter the composition of the microbiome and the risk of infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Tm) in mice. The effect of digoxin treatment on S. Tm infection is transmissible through the microbiome, and characterization of this interaction highlights a digoxin-responsive β-defensin that alters the microbiome composition and consequent immune surveillance of the invading pathogen. Combining epidemiological and experimental approaches thus provides an opportunity to uncover drug–host–microbiome–pathogen interactions that increase the risk of infections in humans.

Date: 2025
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DOI: 10.1038/s41586-025-09273-8

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