Non-antibiotic drugs break colonization resistance against pathogens

Antibiotics facilitate intestinal colonization with pathogens by collaterally damaging the microbiome. Similarly, non-antibiotics can alter the microbiome composition, increasing the risk of gastrointestinal symptoms. Whether this is the result of a direct interaction between non-antibiotic drugs and specific members of the gut microbiome response is unclear. Here, we assessed the impact of non-antibiotic drugs on colonization resistance against pathogenic Gammaproteobacteria. We measured the in vitro growth of Salmonella Typhimurium (S. Tm) in defined synthetic and human stool-derived communities after treatment with non-antibiotics. Multiple treatments altered pathogen growth, mainly promoting its expansion. This was partly explained by the high levels of S. Tm resistance to non-antibiotics, drug-microbe and microbe-microbe interactions and the potential of S. Tm to exploit different metabolic niches. Combined use of certain drugs potentiated S. Tm expansion and most drugs also altered growth of other enteropathogens. S. Tm loads in gnotobiotic and conventional mice increased when treated with drugs that favored pathogen growth in vitro.