Identification of medication-microbiome interactions that affect gut infection

Area of Science:

• Microbiome research
• Infectious disease epidemiology
• Pharmacology

Background:

• Non-antibiotic medications can negatively impact the gut microbiome and intestinal homeostasis.
• Understanding drug effects on the microbiome is crucial for public health.

Purpose of the Study:

• To identify medications associated with an increased risk of gastrointestinal infections.
• To investigate the mechanisms underlying drug-induced alterations in microbiome composition and infection susceptibility.

Main Methods:

• Analysis of a population cohort of over one million individuals monitored for 15 years.
• Experimental studies in mice using Salmonella enterica serovar Typhimurium (S. Tm) infection models.
• Characterization of drug-microbiome-pathogen interactions, including host immune responses.

Main Results:

• Epidemiological data linked specific medications, including digoxin, to a higher risk of gastrointestinal infections.
• Digoxin altered gut microbiome composition and increased susceptibility to S. Tm infection in mice.
• The effects of digoxin on S. Tm infection were transmissible via the microbiome and involved a digoxin-responsive β-defensin.

Conclusions:

• Drug-induced microbiome dysbiosis can increase the risk of infectious diseases.
• Digoxin and potentially other non-antibiotic drugs pose a risk for gastrointestinal infections by altering the gut microbiome and immune surveillance.
• Combined epidemiological and experimental approaches are valuable for uncovering complex drug-host-microbiome-pathogen interactions.