Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.
Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan.
Aliment Pharmacol Ther. 2020 Sep;52(5):821-828. doi: 10.1111/apt.15950. Epub 2020 Jul 20.
Elobixibat, a novel inhibitor of apical sodium-dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function.
To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota.
This was a prospective, single-centre study. After baseline period, patients received 10 mg daily of elobixibat for 2 weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration.
In the 30 patients analysed, the frequency of pre- and post-treatment bowel movements per fortnight was 7 and 10 (P < 0.001), respectively. The pre-treatment faecal bile acid concentration increased significantly from 10.9 to 15.0 µg/g stool post-treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94 µg/g stool to post-treatment 5.02 µg/g stool, P = 0.036) and in glycine-conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels.
Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.
Elobixibat 是一种新型的顶端钠依赖性胆汁酸转运蛋白抑制剂，用于治疗慢性便秘，可增加结肠胆汁酸浓度，刺激肠道功能。然而，尚不清楚哪些胆汁酸发生了变化，或者改变的肠道微生物群是否与可能改变肠道功能的功能效应相关。
研究 Elobixibat 对粪便中总胆汁酸和各胆汁酸浓度以及粪便微生物群的影响。
这是一项前瞻性、单中心研究。在基线期后，患者每天接受 10mg Elobixibat 治疗 2 周。我们评估了 Elobixibat 给药前后对肠道功能、粪便胆汁酸浓度和肠道细菌组成的影响。
在分析的 30 名患者中，治疗前和治疗后每两周的排便频率分别为 7 次和 10 次（P<0.001）。治疗前粪便胆汁酸浓度从治疗前的 10.9μg/g 粪便显著增加到治疗后的 15.0μg/g 粪便（P=0.030），粪便脱氧胆酸显著增加（治疗前 3.94μg/g 粪便，治疗后 5.02μg/g 粪便，P=0.036）和甘氨酸结合的脱氧胆酸和鹅脱氧胆酸。Shannon 指数显著降低，但在属和门水平没有显著变化。
Elobixibat 短期治疗可增加总胆汁酸和脱氧胆酸浓度，降低粪便微生物群多样性。Elobixibat 的生物学效应与其对分泌型胆汁酸的作用有关，而与改变的粪便微生物群的结构变化无关。
