Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.
Effects of Rifaximin on Transit, Permeability, Fecal Microbiome, and Organic Acid Excretion in Irritable Bowel Syndrome.
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DOI：
10.1038/ctg.2016.32
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发表时间：
2016-05-26
影响因子：
3.6
通讯作者：
Fodor A
中科院分区：
文献类型：
--
作者：
Acosta A;Camilleri M;Shin A;Linker Nord S;O'Neill J;Gray AV;Lueke AJ;Donato LJ;Burton DD;Szarka LA;Zinsmeister AR;Golden PL;Fodor A
利福昔明可缓解肠易激综合征 (IBS) 症状、腹胀、腹痛以及稀便或水样便。我们的目的是调查利福昔明治疗的 IBS 患者的消化功能。在一项随机、双盲、安慰剂对照、平行组研究中，我们比较了利福昔明 550 mg tid 和安慰剂 14 天对非便秘 IBS 的影响，且无小肠细菌过度生长 (SIBO) 的证据。所有受试者均通过闪烁扫描完成了结肠运输的基线和治疗评估，通过乳果糖-甘露醇排泄进行了粘膜通透性评估，并通过随机粪便样本测量了粪便微生物组、胆汁酸和短链脂肪酸。使用意向治疗协方差分析（ANCOVA，以基线值作为协变量）评估治疗组之间主要缓解措施的总体比较。治疗对 24 小时肠道症状、小肠或结肠通透性或结肠传输没有显着影响。利福昔明与升结肠排空加速（安慰剂14.9±2.6小时；利福昔明6.9±0.9小时；P=0.033）和48小时时的整体结肠传输加速相关（几何中心4.0±0.3小时安慰剂；利福昔明4.7±0.2小时；P=0.046）；然而，利福昔明并没有显着改变每克粪便中的总粪便胆汁酸或粪便中单独胆汁酸或乙酸盐、丙酸盐或丁酸盐的比例。微生物组研究显示，受试者内部存在很强的关联，与受试者之间的时间存在适度的关联，微生物丰富度与治疗组（利福昔明与治疗）之间存在微小但显着的关联。对于无 SIBO 记录的非便秘 IBS，利福昔明治疗与结肠运输加速和微生物丰富度变化相关；报告的症状获益机制需要进一步研究。
Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose–mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.