Drug-microbiome-host interactions: antimicrobial effects of non-antibiotic compounds

Antibiotics have traditionally been defined as drugs that specifically target and inhibit pathogenic bacteria, forming the cornerstone of infectious disease treatment. However, resent research has expanded our understanding of what constitutes an antimicrobial substance. Many compounds not classified as antibiotics - including common pharmaceuticals, dietary substances, and agricultural or industrial chemicals - have been shown to exhibit antibacterial activity. Intriguingly, these non-antibiotic compounds often exert stronger effects on beneficial bacteria than on members of the Enterobacteriaceae family, which includes many classic pathogens for which new antibiotics are urgently needed. The selective pressure imposed by non-antibiotic antimicrobials can disrupt the balance of the human microbiome and create conditions favouring resistant or opportunistic pathogens. Such imbalances have implications not only for infectious disease but also for a range of chronic, non-communicable health conditions and the spread of antimicrobial resistances. In this Review, we highlight the latest advances in understanding the molecular mechanisms by which non-antibiotic compounds exert antimicrobial effects and examine key factors that modulate their activity. Lastly, we highlight the implications for translation and clinical practice.