Uji Masahito, Yokoyama Yukihiro, Asahara Takashi, Ebata Tomoki, Igami Tsuyoshi, Mizuno Takashi, Yamaguchi Junpei, Nagino Masato
Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yakult Central Institute, Tokyo, Japan.
Hepatol Res. 2018 Feb;48(3):E303-E310. doi: 10.1111/hepr.12985. Epub 2017 Nov 1.
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.
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.
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.
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.
茵陈蒿汤(ICKT)作为一种具有肝脏保护作用的草药,其利胆作用在患者中存在差异。本研究旨在探讨ICKT的利胆作用与胆道梗阻患者肠道微环境之间的相关性。
纳入接受体外胆道引流的胆道梗阻患者。测量ICKT治疗前后胆汁中总胆红素和胆汁酸的浓度,以及血液中ICKT的主要活性成分京尼平的浓度。收集患者粪便以确定细菌计数和有机酸浓度。
收集并分析了37例患者的样本。ICKT治疗后3小时,血清京尼平浓度升高,且与胆汁酸、总胆红素和直接胆红素的胆汁浓度变化百分比呈正相关。血清京尼平浓度还与粪便中代表性专性厌氧菌如纤细梭菌亚群、脆弱拟杆菌群、双歧杆菌和阿托波菌属的浓度呈正相关。形成鲜明对比的是,艰难梭菌、肠杆菌科和肠球菌等所谓的有害细菌与京尼平浓度呈负相关。ICKT给药后京尼平浓度与粪便中丙酸和丁酸等短链脂肪酸浓度呈正相关,与粪便中乳酸浓度呈负相关。
患者对京尼平的吸收存在差异。这种差异可能与粪便微环境特征有关,部分解释了ICKT在患者中利胆作用的差异。