Double-Blind Randomized Controlled Trial of Rifaximin for Persistent Symptoms in Patients with Celiac Disease

  • Matthew S. Chang
  • Maria T. Minaya
  • Jianfeng Cheng
  • Bradley A. Connor
  • Suzanne K. Lewis
  • Peter H. R. Green
Original Article



Small intestinal bacterial overgrowth (SIBO) is one cause of a poor response to a gluten-free diet (GFD) and persistent symptoms in celiac disease. Rifaximin has been reported to improve symptoms in non-controlled trials.


To determine the effect of rifaximin on gastrointestinal symptoms and lactulose-hydrogen breath tests in patients with poorly responsive celiac disease.


A single-center, double-blind, randomized, controlled trial of patients with biopsy-proven celiac disease and persistent gastrointestinal symptoms despite a GFD was conducted. Patients were randomized to placebo (n = 25) or rifaximin (n = 25) 1,200 mg daily for 10 days. They completed the Gastrointestinal Symptom Rating Scale (GSRS) and underwent lactulose-hydrogen breath tests at weeks 0, 2, and 12. An abnormal breath test was defined as: (1) a rise in hydrogen of ≥20 parts per million (ppm) within 100 min, or (2) two peaks ≥20 ppm over baseline.


GSRS scores were unaffected by treatment with rifaximin, regardless of baseline breath tests. In a multivariable regression model, the duration of patients’ gastrointestinal symptoms significantly predicted their overall GSRS scores (estimate 0.029, p < 0.006). According to criteria 1 and 2, respectively, SIBO was present in 55 and 8% of patients at baseline, intermittently present in 28 and 20% given placebo, and 28 and 12% given rifaximin. There was no difference in the prevalence of SIBO between placebo and treatment groups at weeks 2 and 12.


Rifaximin does not improve patients’ reporting of gastrointestinal symptoms and hydrogen breath tests do not reliably identify who will respond to antibiotic therapy.


Celiac disease Small intestine Clinical pharmacology Diarrhea Malabsorption Microbiology Symptom score or index 



This study was funded in part by Salix Pharmaceuticals who provided the study medication and placebo. The preparation of this paper, including data analysis and writing, was not funded and was conducted by the authors exclusively.

Conflict of interest

Drs. Peter Green, Matthew Chang, Maria Minaya, Jianfeng Cheng, Bradley Connor, Suzanne Lewis have no personal interests to declare.


  1. 1.
    Green P, Cellier C. Celiac disease. N Engl J Med. 2007;357:1731–1743.PubMedCrossRefGoogle Scholar
  2. 2.
    O’Mahony S, Howdle P, Losowsky M. Review article: management of patients with non-responsive coeliac disease. Aliment Pharmacol Ther. 1996;10:671–680.PubMedCrossRefGoogle Scholar
  3. 3.
    Abdallah H, Leffler D, Dennis M, Kelly C. Refractory celiac disease. Curr Gastroenterol Rep. 2007;9:401–405.PubMedCrossRefGoogle Scholar
  4. 4.
    Fine KD, Meyer RL, Lee EL. The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet. Gastroenterology. 1997;112:1830–1838.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubio-Tapia A, Barton SH, Rosenblatt JE, Murray JA. Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease. J Clin Gastroenterol. 2009;43:157–161.PubMedCrossRefGoogle Scholar
  6. 6.
    Tursi A, Brandimarte G, Giorgetti G. High prevalence of small intestinal bacterial overgrowth in celiac patients with persistence of gastrointestinal symptoms after gluten withdrawal. Am J Gastroenterol. 2003;98:839–843.PubMedCrossRefGoogle Scholar
  7. 7.
    Rana SV, Sinha SK, Lal S, Sikander A, Singh K. Small intestinal bacterial overgrowth in North Indian patients with celiac disease. Trop Gastroenterol. 2007;28:159–161.PubMedGoogle Scholar
  8. 8.
    Abdulkarim AS, Burgart LJ, See J, Murray JA. Etiology of nonresponsive celiac disease: results of a systematic approach. Am J Gastroenterol. 2002;97:2016–2021.PubMedCrossRefGoogle Scholar
  9. 9.
    Prizont R, Hersh T, Floch MH. Jejunal bacterial flora in chronic small bowel disease. I. Celiac disease. II. Regional enteritis. Am J Clin Nutr. 1970;23:1602–1607.PubMedGoogle Scholar
  10. 10.
    Quigley E, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006;130:S78–S90.PubMedCrossRefGoogle Scholar
  11. 11.
    Rana S, Bhardwaj S. Small intestinal bacterial overgrowth. Scand J Gastroenterol. 2008;43:1030–1037.PubMedCrossRefGoogle Scholar
  12. 12.
    Corazza G, Menozzi M, Strocchi A, et al. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology. 1990;98:302–309.PubMedGoogle Scholar
  13. 13.
    Ghoshal U, Ghoshal U, Misra A, Choudhuri G. Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance. BMC Gastroenterol. 2004;10.Google Scholar
  14. 14.
    Roufail WM, Ruffin JM. Effect of antibiotic therapy on gluten-sensitive enteropathy. Am J Dig Dis. 1966;11:587–593.PubMedCrossRefGoogle Scholar
  15. 15.
    Pelosini I, Scarpignato C. Rifaximin, a peculiar rifamycin derivative: established and potential clinical use outside the gastrointestinal tract. Chemotherapy. 2005;122–130.Google Scholar
  16. 16.
    Lauritano E, Gabrielli M, Lupascu A, et al. Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2005;22:31–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Scarpellini E, Gabrielli M, Lauritano E, et al. High-dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2007;25:781–786.Google Scholar
  18. 18.
    Svedlund J, Sjodin I, Dotevall G. GSRS—a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33:129–134.Google Scholar
  19. 19.
    Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I. A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence. Am J Gastroenterol. 2006;101:326–333.PubMedCrossRefGoogle Scholar
  20. 20.
    Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412–419.PubMedGoogle Scholar
  21. 21.
    Corazza GR, Strocchi A, Gasbarrini G. Fasting breath hydrogen in celiac disease. Gastroenterology. 1987;93:53–58.PubMedGoogle Scholar
  22. 22.
    Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000;95:3503–3506.PubMedCrossRefGoogle Scholar
  23. 23.
    Walters B, Vanner SJ. Detection of bacterial overgrowth in IBS using the lactulose H2 breath test: comparison with 14C-D-xylose and healthy controls. Am J Gastroenterol. 2005;100:1566–1570.PubMedCrossRefGoogle Scholar
  24. 24.
    Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009;18:349–358.PubMedCrossRefGoogle Scholar
  25. 25.
    Mustalahti K, Lohiniemi S, Collin P, Vuolteenaho N, Laippala P, Mäki M. Gluten-free diet and quality of life in patients with screen-detected celiac disease. Eff Clin Pract. 2002;5:105–113.PubMedGoogle Scholar
  26. 26.
    Lohiniemi S, Mäki M, Kaukinen K, Laippala P, Collin P. Gastrointestinal symptoms rating scale in coeliac disease patients on wheat starch-based gluten-free diets. Scand J Gastroenterol. 2000;35:947–949.PubMedCrossRefGoogle Scholar
  27. 27.
    Hallert C, Granno C, Grant C, et al. Quality of life of adult coeliac patients treated for 10 years. Scand J Gastroenterol. 1998;33:933–938.PubMedCrossRefGoogle Scholar
  28. 28.
    Hopman EG, Koopman HM, Wit JM, Mearin ML. Dietary compliance and health-related quality of life in patients with coeliac disease. Eur J Gastroenterol Hepatol. 2009;21:1056–1061.PubMedCrossRefGoogle Scholar
  29. 29.
    Nachman F, Vazquez H, Gonzalez A, et al. Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet. Clin Gastroenterol Hepatol. 2011;9:214–219.PubMedCrossRefGoogle Scholar
  30. 30.
    Midhagen G, Hallert C. High rate of gastrointestinal symptoms in celiac patients living on a gluten-free diet: controlled study. Am J Gastroenterol. 2003;98:2023–2026.PubMedCrossRefGoogle Scholar
  31. 31.
    Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.PubMedCrossRefGoogle Scholar
  32. 32.
    Leffler D, Dennis M, Hyett B, Kelly E, Schuppan D, Kelly C. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol. 2007;5:445–450.PubMedCrossRefGoogle Scholar
  33. 33.
    Dorn SD, Hernandez L, Minaya MT, et al. Psychosocial factors are more important than disease activity in determining gastrointestinal symptoms and health status in adults at a celiac disease referral center. Dig Dis Sci. 2010;55:3154–3163.PubMedCrossRefGoogle Scholar
  34. 34.
    Gasbarrini A, Lauritano E, Gabrielli M, et al. Small intestinal bacterial overgrowth: diagnosis and treatment. Dig Dis. 2007;25:237–240.PubMedCrossRefGoogle Scholar
  35. 35.
    Khoshini R, Dai SC, Lezcano S, Pimentel M. A systematic review of diagnostic tests for small intestinal bacterial overgrowth. Dig Dis Sci. 2008;53:1443–1454.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Matthew S. Chang
    • 1
  • Maria T. Minaya
    • 1
  • Jianfeng Cheng
    • 2
  • Bradley A. Connor
    • 3
  • Suzanne K. Lewis
    • 1
  • Peter H. R. Green
    • 1
  1. 1.Department of MedicineColumbia University College of Physicians and SurgeonsNew YorkUSA
  2. 2.Department of MedicineVirginia Commonwealth UniversityRichmondUSA
  3. 3.Department of MedicineWeill Medical College of Cornell UniversityNew YorkUSA

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