Impacts of Medications on Microbiome-mediated Protection against Enteric Pathogens

Area of Science:

• Microbiology
• Pharmacology
• Gastroenterology

Background:

• The majority of individuals in the U.S. use prescription drugs for health management.
• Non-antibiotic medications can disrupt the gut microbiome and intestinal homeostasis.
• Understanding drug-microbiome interactions is crucial for preventing infections.

Purpose of the Study:

• To identify medications associated with an increased risk of gastrointestinal (GI) infections.
• To investigate the impact of specific drugs, like digoxin, on gut microbiome composition and infection risk.
• To elucidate the mechanisms underlying drug-induced alterations in host-microbiome-pathogen interactions.

Main Methods:

• Epidemiological analysis of a population cohort exceeding 1 million individuals over 15 years.
• Experimental studies in mice to assess the effect of digoxin on Salmonella enterica subsp. Typhimurium (S. Tm) infection.
• Microbiome characterization and analysis of host-pathogen interactions, including immune surveillance pathways.

Main Results:

• Several non-antibiotic medications were linked to an elevated risk of GI infections.
• Digoxin was identified as a drug that alters gut microbiome composition and increases S. Tm infection risk in mice.
• The effect of digoxin on S. Tm infection was shown to be transmissible through the microbiome, involving a digoxin-responsive β-defensin.

Conclusions:

• Non-antibiotic medications can significantly impact the gut microbiome and increase susceptibility to GI pathogens.
• Digoxin's effects on the microbiome and infection risk highlight a specific drug-host-microbiome-pathogen interaction.
• Integrated epidemiological and experimental approaches are valuable for uncovering drug-induced infection risks.