Does the intestinal microenvironment have an impact on the choleretic effect of inchinkoto, a hepatoprotective herbal medicine?

Aim: The choleretic effects of inchinkoto (ICKT), a hepatoprotective herbal medicine, are variable among patients. This study sought to investigate the correlation between the choleretic effects of ICKT and the intestinal microenvironment in patients with biliary obstruction. Methods: Patients with biliary obstruction who underwent external biliary drainage were enrolled. The concentrations of total bilirubin and bile acid in the bile, and genipin, a major active ingredient of ICKT, in the bloodstream before and after ICKT treatment were measured. Feces were collected from the patients to determine bacterial count and organic acid concentrations. Results: Samples from 37 patients were collected and analyzed. The serum concentration of genipin increased 3 h after ICKT treatment and showed a positive correlation with the percent changes of biliary concentrations of bile acid, total bilirubin, and direct bilirubin. Serum genipin concentration also showed a positive correlation with the fecal concentrations of representative obligate anaerobes such as the Clostridium leptum subgroup, Bacteroides fragilis group, Bifidobacterium, and the Atopobium cluster. In sharp contrast, so-called harmful bacteria such as Clostridium difficile, Enterobacteriaceae, and Enterococcus showed a negative correlation with the concentration of genipin. Genipin concentration after ICKT administration showed a positive correlation with the fecal concentration of short chain fatty acids such as propionic acid and butyric acid, and a negative correlation with the fecal concentration of lactic acid. Conclusions: The absorption of genipin was variable among patients. This variability may be associated with the fecal microenvironment profile and partly explain the variable choleretic effects of ICKT among patients.