The study investigates the impact of non-antibiotic drugs on the human gut microbiome. Researchers screened over 1000 marketed drugs against 40 representative gut bacterial strains and found that 24% of human-targeted drugs inhibited the growth of at least one strain, with particular classes like antipsychotics being overrepresented. The effects of these drugs on gut bacteria are reflected in their antibiotic-like side effects in humans, as seen in existing cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting that non-antibiotics may promote antibiotic resistance. The findings provide a comprehensive resource for future research on drug-microbiome interactions, opening new avenues for side effect control, drug repurposing, and understanding antibiotic resistance.The study investigates the impact of non-antibiotic drugs on the human gut microbiome. Researchers screened over 1000 marketed drugs against 40 representative gut bacterial strains and found that 24% of human-targeted drugs inhibited the growth of at least one strain, with particular classes like antipsychotics being overrepresented. The effects of these drugs on gut bacteria are reflected in their antibiotic-like side effects in humans, as seen in existing cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting that non-antibiotics may promote antibiotic resistance. The findings provide a comprehensive resource for future research on drug-microbiome interactions, opening new avenues for side effect control, drug repurposing, and understanding antibiotic resistance.