Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre-fecal Microbiota Transplantation Evaluation?
Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms.
This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm within 90 min. The presence of GI symptoms and CDI resolution were assessed 8 weeks post-FMT. Fisher’s exact/Student’s t tests were performed for statistical analyses.
Twenty recipients (58.3 years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p = 0.09).
FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.
KeywordsClostridium difficile Fecal microbiota transplantation Small intestinal bacterial overgrowth Lactulose breath test Diarrhea
JRA and WWC initiated study concept and design. JRA contributed to acquisition of data, analysis and interpretation of data, and drafting of the manuscript. ZK and WWC contributed to interpretation of data and critical revision of the manuscript.
Compliance with ethical standards
Conflict of interest
ZK is employed at OpenBiome, a nonprofit stool bank that provides clinicians with preparations for fecal microbiota transplantation and supports research into the human microbiome. ZK also receives research support and has equity in Finch Therapeutics. JRA consults for Finch Therapeutics. There were no other conflicts of interest to report for any authors relevant to the work presented in this manuscript.
- 1.Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198–1208. https://doi.org/10.1056/NEJMoa1306801.
- 2.Lessa FC, Mu Y, Bamberg WM, et al. Burden of clostridium difficile infection in the united states. N Engl J Med. 2015;372:825–834. https://doi.org/10.1056/NEJMoa1408913.
- 3.Kassam Z, Lee CH, Hunt RH. Review of the emerging treatment of clostridium difficile infection with fecal microbiota transplantation and insights into future challenges. Clin Lab Med. 2014;34:787–798. https://doi.org/10.1016/j.cll.2014.08.007.
- 4.AlNahhas F, Wadhwa A, Khanna S, et al. Epidemiology of post infectious irritable bowel syndrome following clostridium difficile infection. United European Gastroenterol J. 2015;3:A131.Google Scholar
- 5.Ghoshal UC, Ranjan P. Post-infectious irritable bowel syndrome: The past, the present and the future. J Gastroenterol Hepatol. 2011;26:94–101. https://doi.org/10.1111/j.1440-1746.2011.06643.x.
- 6.Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for clostridium difficile infection: Systematic review and meta-analysis. Am J Gastroenterol. 2013;108:500–508. https://doi.org/10.1038/ajg.2013.59.
- 7.Smith M, Kassam Z, Edelstein C, Burgess J, Alm E. OpenBiome remains open to serve the medical community. Nat Biotechnol. 2014;32:867. https://doi.org/10.1038/nbt.3006.
- 8.Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent clostridium difficile infection. Am J Gastroenterol. 2012;107:761–767. https://doi.org/10.1038/ajg.2011.482.
- 9.Bakken JS, Borody T, Brandt LJ, et al. Treating clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044–1049. https://doi.org/10.1016/j.cgh.2011.08.014.
- 10.Dubois N, Ling K, Osman M, et al. Prospective assessment of donor eligibility for fecal microbiota transplantation at a public stool bank: Results from the evaluation of 1387 candidate donors. Open Forum Infect Dis. 2016;2:962.Google Scholar
- 11.Pamer EG. Fecal microbiota transplantation: Effectiveness, complexities, and lingering concerns. Mucosal Immunol. 2014;7:210–214. https://doi.org/10.1038/mi.2013.117.
- 12.Kassam Z, Hundal R, Marshall JK, Lee CH. Fecal transplant via retention enema for refractory or recurrent clostridium difficile infection. Arch Intern Med. 2012;172:191–193. https://doi.org/10.1001/archinte.172.2.191.
- 13.van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent clostridium difficile. N Engl J Med. 2013;368:407–415. https://doi.org/10.1056/NEJMoa1205037.
- 14.Stollman N, Smith M, Giovanelli A, et al. Frozen encapsulated stool in recurrent clostridium difficile: Exploring the role of pills in the treatment hierarchy of fecal microbiota transplant nonresponders. Am J Gastroenterol. 2015;110:600–601. https://doi.org/10.1038/ajg.2015.81.
- 15.Fischer M, Allegretti J, Smith M, et al. A multi-center, cluster randomized dose-finding study of fecal microbiota transplantation capsules for recurrent clostridium difficile infection. European Gastroenterol J. 2015;3:A1–A685.Google Scholar
- 16.Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent clostridium difficile infection: A randomized clinical trial. JAMA. 2016;315:142–149. https://doi.org/10.1001/jama.2015.18098.
- 17.Chang BW, Rezaie A. Irritable bowel syndrome-like symptoms following fecal microbiota transplantation: A possible donor-dependent complication. Am J Gastroenterol. 2017;112:186–187. https://doi.org/10.1038/ajg.2016.472.
- 18.Rezaie A, Buresi M, Lembo A, et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: The North American consensus. Am J Gastroenterol. 2017;112:775–784. https://doi.org/10.1038/ajg.2017.46.
- 19.Hawkey C, Bosch K, Richter J, eds. Textbook of Clinical Gastroenterology and Hepatology. Hoboken, NJ: Wiley; 2012.Google Scholar
- 20.Donald IP, Kitchingmam G, Donald F, Kupfer RM. The diagnosis of small bowel bacterial overgrowth in elderly patients. J Am Geriatr Soc. 1992;40:692–696.Google Scholar
- 21.Bratten JR, Spanier J, Jones MP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol. 2008;103:958–963. https://doi.org/10.1111/j.1572-0241.2008.01785.x.