Non-antibiotics disrupt colonization resistance against enteropathogens

Area of Science:

• Microbiology
• Pharmacology
• Gastroenterology

Background:

• Non-antibiotic medications can alter gut microbiome composition.
• The health implications of these alterations are largely unknown.
• Understanding drug effects on gut microbial communities is crucial.

Purpose of the Study:

• To investigate how non-antibiotics impact gut commensals' resistance to enteropathogen colonization.
• To develop an in vitro assay for assessing enteropathogen growth in drug-altered microbial communities.

Main Methods:

• Utilized an in vitro assay to test 53 non-antibiotic drugs on microbial communities.
• Assessed pathogen growth in synthetic and human stool-derived communities.
• Evaluated the effect of specific drugs on Salmonella Typhimurium (S. Tm) colonization in mice.

Main Results:

• 28% of tested non-antibiotics increased S. Tm growth by inhibiting commensals and altering microbial interactions.
• Pathogenic bacteria showed higher resistance to non-antibiotics than commensals.
• In vivo studies confirmed that drugs promoting pathogen expansion increased intestinal S. Tm load.

Conclusions:

• Non-antibiotics can disrupt colonization resistance, favoring pathogen expansion.
• The antihistamine terfenadine accelerated S. Tm-induced disease and inflammation in mice.
• Non-antibiotic drugs are identified as overlooked risk factors for enteric infections.