Role of the gut microbiota in the pharmacological effects of traditional Kampo medicine and natural products.

The human gastrointestinal tract harbors over a thousand coexisting bacterial species that together constitute a highly complex intestinal microbiome. Dysbiosis of this microbial ecosystem has been implicated in the pathogenesis of disorders such as ulcerative colitis and obesity and has driven the development of microbiota-targeted prevention and treatment strategies. Traditional Kampo medicines are used with the aim of restoring the balance of the whole body, having been developed and established uniquely in Japan based on traditional Chinese medicine with a history of over two millennia. Recent evidence has revealed that the gut microbiota plays critical roles in the pharmacological effects of traditional Kampo medicines. For example, the anti-obesity activity of Bofutsushosan has been linked to an increase in Akkermansia muciniphila. The laxative effect of Daiokanzoto is related to rheinanthrone, which is produced from sennoside A through the gut microbiota, and drugs and foods that can alter the gut microbiota change the laxative activity of Daiokanzoto. In recent years, clinical trials have been conducted to examine the relationship between changes in the gut microbiota and the pharmacological effects of Kampo medicines, and this relationship has come to the forefront. This review discusses the findings of basic and clinical research on the role of the gut microbiota in the pharmacological action of traditional Kampo medicines, focusing on Bofutsushosan, Daiokanzoto, Daikenchuto, and Hangeshashinto, and discusses future issues and prospects for research into these interactions.