Metabolic Insights into Gut Microbiota in the Pharmacology of Natural Medicines (Accepted)

Natural medicines (NMs) show unique advantages in the clinical management of chronic diseases. Recent years have witnessed an increasing consensus on the role of gut microbiota in the efficacy and synergy of NMs, which has given new impetus to elucidating the material basis and mechanisms of NMs and the way towards modernization. A bottom question that has emerged is how the NM-microbiota interactions are integrated into the multi-target holistic mechanisms of NMs, the answer to which may also shed new light on the road of new drug discovery. Metabolic regulation via small-molecule metabolites has been increasingly implicated in host-microbe interaction. In this review, we provide an integral metabolic perspective on NMs-microbiota interaction in host health and disease. We highlight the emerging understanding of gut microbiota-related metabolic signals implicated in NM components' local and systemic actions. We also discuss key issues and prospects related to drug development and the translational study of NMs.