{Reference Type}: Journal Article {Title}: Gut microbiome-derived hydrolases-an underrated target of natural product metabolism. {Author}: He J;Liu X;Zhang J;Wang R;Cao X;Liu G; {Journal}: Front Cell Infect Microbiol {Volume}: 14 {Issue}: 0 {Year}: 2024 {Factor}: 6.073 {DOI}: 10.3389/fcimb.2024.1392249 {Abstract}: In recent years, there has been increasing interest in studying gut microbiome-derived hydrolases in relation to oral drug metabolism, particularly focusing on natural product drugs. Despite the significance of natural product drugs in the field of oral medications, there is a lack of research on the regulatory interplay between gut microbiome-derived hydrolases and these drugs. This review delves into the interaction between intestinal microbiome-derived hydrolases and natural product drugs metabolism from three key perspectives. Firstly, it examines the impact of glycoside hydrolases, amide hydrolases, carboxylesterase, bile salt hydrolases, and epoxide hydrolase on the structure of natural products. Secondly, it explores how natural product drugs influence microbiome-derived hydrolases. Lastly, it analyzes the impact of interactions between hydrolases and natural products on disease development and the challenges in developing microbial-derived enzymes. The overarching goal of this review is to lay a solid theoretical foundation for the advancement of research and development in new natural product drugs and personalized treatment.