TY - JOUR
T1 - Effects of rifaximin on transit, permeability, fecal microbiome, and organic acid excretion in irritable bowel syndrome
AU - Acosta, Andres
AU - Camilleri, Michael
AU - Shin, Andrea
AU - Nord, Sara Linker
AU - Neill, Jessica O.
AU - Gray, Amber V.
AU - Lueke, Alan J.
AU - Donato, Leslie J.
AU - Burton, Duane D.
AU - Szarka, Lawrence A.
AU - Zinsmeister, Alan R.
AU - Golden, Pamela L.
AU - Fodor, Anthony
N1 - Funding Information:
Guarantor of the article: Michael Camilleri, MD. Specific author contributions: A. Acosta and A. Shin: fellow, patient recruitment, and management. M. Camilleri: principal investigator, conceptualization, analysis and interpretation, authorship of manuscript. S. Linker Nord and J. O’Neill: study coordinators. A.V. Gray and A.J. Lueke: analysis of stool bile acids. L.J. Donato: laboratory medicine supervision for stool analyses. D.D. Burton: transit measurements. L.A. Szarka: staff co-investigator involved in patient care. A.R. Zinsmeister: study biostatistician. P.L. Golden: study conceptualization with principal investigator. A. Fodor: microbiome analysis and interpretation. All authors had access to the study data and reviewed and approved the final manuscript. Financial support: This study was supported by a research grant from Salix Pharmaceuticals. Potential competing interests: M. Camilleri has attended one advisory board meeting for Salix in the past 5 years with compensation to his employer, Mayo Clinic, and no personal financial remuneration. Anthony Fodor has served, and continues to serve, as a consultant to Salix Pharmaceuticals. Pamela L. Golden is a former employee of Salix Pharmaceuticals.
Publisher Copyright:
© 2016 Lippincott Williams and Wilkins. All rights reserved.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - OBJECTIVES: 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. METHODS: 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). RESULTS: 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 (14.92.6 h placebo; 6.90.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.00.3 h placebo; 4.70.2 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). CONCLUSIONS: 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.
AB - OBJECTIVES: 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. METHODS: 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). RESULTS: 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 (14.92.6 h placebo; 6.90.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.00.3 h placebo; 4.70.2 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). CONCLUSIONS: 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.
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U2 - 10.1038/ctg.2016.32
DO - 10.1038/ctg.2016.32
M3 - Article
AN - SCOPUS:85122939744
VL - 7
JO - Clinical and Translational Gastroenterology
JF - Clinical and Translational Gastroenterology
SN - 2155-384X
IS - 5
M1 - e173
ER -