Identification of medication-microbiome interactions that impact gut infection

The majority of people in the U.S. manage health through at least one prescription drug. Drugs classified as non-antibiotics can adversely affect the gut microbiome and disrupt intestinal homeostasis. Here, we identified medications associated with an increased risk of GI infections across a population cohort of more than 1 million individuals monitored over 15 years. Notably, the cardiac glycoside digoxin and other drugs identified in this epidemiological study are sufficient to alter microbiome composition and risk of Salmonella enterica subsp. Typhimurium (S. Tm) infection in mice. The impact of digoxin treatment on S. Tm infection is transmissible via the microbiome, and characterization of this interaction highlights a digoxin-responsive b-defensin that alters 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 infection risk in human populations. We characterized the effect of digoxin on gene expression of mice ileum tissue. We treated conventional C57BL/6NTac mice with 4 doses of digoxin orally over two days. Mice were sacrificed at D0 time point and approximately 2cm of terminal ileum tissue was collected. RNA was extracted and samples were sent for bulk-RNA sequencing. PBS dissolved in 5% DMSO was used as vehicle controls. Three biological replicates were used for the experiment