The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota
The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota
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DOI：
10.1111/apt.15950
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发表时间：
2020-07-20
影响因子：
7.6
通讯作者：
Camilleri, Michael
中科院分区：
文献类型：
--
作者：
Misawa, Noboru;Higurashi, Takuma;Camilleri, Michael
依洛昔巴特是一种新型的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，刺激肠功能。然而，目前尚不清楚哪些胆汁酸被改变，或者肠道微生物群的改变是否与可能改变肠道功能的功能效应有关。目的研究依洛昔巴特不仅对总胆汁酸的粪便浓度变化，而且对单个胆汁酸和粪便微生物群的影响。方法本研究为前瞻性、单中心研究。基线期后，患者接受10 mg每日依洛昔巴特治疗2周。我们评估了依洛昔巴特给药前后对肠功能、粪便胆汁酸浓度和肠道细菌组成的变化的影响。结果30例患者治疗前后每2周排便次数分别为7次和10次（P < 0.001）。治疗前粪便胆汁酸浓度从10.9 μ g/g粪便显著增加至治疗后15.0 μ g/g粪便（P = 0.030），粪便脱氧胆酸（治疗前3.94 μ g/g粪便至治疗后5.02 μ g/g粪便，P = 0.036）以及甘氨酸结合脱氧胆酸和鹅脱氧胆酸显著增加。Shannon指数显著降低，但在属和门水平上没有显著变化。结论依洛昔巴特短期治疗可增加总胆汁酸和脱氧胆酸的浓度，降低粪便微生物群的多样性。依洛昔巴特的生物学效应与其对分泌性胆汁酸的影响有关，而不是改变粪便微生物群的结构变化。
Background 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. Aims To investigate the effects of elobixibat on changes not only in the faecal concentrations of total but also in individual bile acids and in faecal microbiota. Methods 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. Results 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 mu g/g stool post-treatment (P = 0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94 mu g/g stool to post-treatment 5.02 mu g/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. Conclusions 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.