Chronic diseases encompass a wide range of illnesses, ranging from cardiovascular and cerebrovascular diseases, metabolic syndromes to degenerative neurological disorders. Chronic diseases are responsible for most observed morbidity and mortality in the developed countries as well as in some developing countries. The gut microbiota and its metabolites have been associated with the onset and development of chronic diseases such as coronary heart diseases and metabolic disorders, and the delineation of the underlying mechanisms makes the gut microbiome “druggable”, i.e., providing novel therapeutic potential of treating chronic diseases through manipulating gut microbiota. Recent research findings provide a variety of new and critical molecular mechanistic insights into the causal link between the gut microbiome and the antichronic disease efficacy of natural products developed from traditional Chinese medicine, e.g., berberine. These medicinal agents, although often with low oral bioavailability, show therapeutic efficacy through targeting both symptoms and root causes of chronic diseases. CLICK TO REVIEW