Targeting the human gut microbiome with small-molecule inhibitors

The human gut microbiome is a complex microbial community that is strongly linked to both host health and disease. However, the detailed molecular mechanisms underlying the effects of these microorganisms on host biology remain largely uncharacterized. The development of non-lethal, small-molecule inhibitors that target specific gut microbial activities enables a powerful but underutilized approach to studying the gut microbiome and a promising therapeutic strategy. In this Review, we will discuss the challenges of studying this microbial community, the historic use of small-molecule inhibitors in microbial ecology, and recent applications of this strategy. We also discuss the evidence suggesting that host-targeted drugs can affect the growth and metabolism of gut microbes. Finally, we address the issues of developing and implementing microbiome-targeted small-molecule inhibitors and define important future directions for this research.