Abstract

Rifaximin is associated with modest, transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome

Fodor AA1, Pimentel M2, Chey WD3, Lembo A4, Golden PL5, Israel RJ5, Carroll IM6. Gut Microbes. 2018 Apr 30:1-28. doi: 10.1080/19490976.2018.1460013. [Epub ahead of print]
 
     

Author information

1 a Department of Bioinformatics and Genomics , University of North Carolina at Charlotte , Charlotte , North Carolina , USA.

2 b Division of Gastroenterology, Cedars-Sinai Medical Center , Los Angeles , California , USA.

3 c Division of Gastroenterology, Michigan Medicine , Ann Arbor , Michigan , USA.

4 d Division of Gastroenterology, Beth Israel Deaconess Medical Center , Boston , Massachusetts , USA.

5 e Nonclinical and Clinical Pharmacology, Clinical and Medical Affairs, Salix Pharmaceuticals , Bridgewater , New Jersey , USA*.

6 f Department of Nutrition and Division of Gastroenterology and Hepatology , University of North Carolina , Chapel Hill , North Carolina , USA.

Abstract

Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.

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