Fecal Microbiota Transplantation Inducing Remission in Crohn’s Colitis and the Associated Changes in Fecal Microbial Profile Dina Kao, MD, FRCPC,* Naomi Hotte, MSc,* Patrick Gillevet, PhD,w and Karen Madsen, PhD* Abstract: Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine of unclear etiology. Increasing evidence has pointed to intestinal dysbiosis as a potential factor in a genetically susceptible individual. Fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease with variable degrees of success. Herein, we report a patient with Crohn’s colitis, previously failing an immunosuppressant, who achieved clinical, endoscopic, and histologic remission after a single fecal microbiota trans- plantation infusion. We have further characterized the changes in the fecal microbiota associated with this observation. Key Words: inflammatory bowel disease (IBD), fecal microbiota transplantation (FMT), mucosal healing, dysbiosis (J Clin Gastroenterol 2014;48:625–628) I nflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder of unknown etiology. There is increasing evidence suggesting that genetics, environmental factors, and intestinal dysbiosis are implicated in its pathogenesis. Although gut dysbiosis has been well descri- bed in patients with IBD, it is unclear whether these changes are causative or associative. 1 Fecal microbiota transplantation (FMT) has been used to treat recurrent Clostridium difficile infections (CDI) with an overall cure rate of over 80% after a single infu- sion. 2,3 In these cases, fecal microbiota analyses demon- strated a restoration of bacterial flora characterized by an increase in biodiversity, stability, and a remarkable resem- blance to donor’s profile following FMT. 4 As early as 1989, FMT has also been used to treat IBD, sometimes with dramatic responses. 5,6 Borody and Campbell 7 reported using FMT as an induction and maintenance therapy, with as many as 69 rectal infusions, to successfully treat 3 patients with IBD. However, in most cases, the results are not as consistent or as durable as in the setting of CDI. Most of the published reports consist of small case series, which suffer from significant heterogeneity with regard to disease activity, mode and frequency of delivery, and duration of follow-up. A systematic review published in 2012 included 9 case series/reports of FMT to treat IBD (N = 26); it found that 19/25 patients experienced symptomatic improvement, 13/17 ceased taking IBD med- ications within 6 weeks, and 15/24 had no active disease 3 to 36 months after FMT. 8 A recent case series also found that 7/9 pediatric patients with mild-to-moderate UC dis- ease activity experienced clinical improvement, and 3/9 achieved clinical remission within 1 week after a 5-day course of daily FMT enema (daily volume of 240 mL). 9 In contrast, another pilot study examined the role of FMT in the management of 4 patients with refractory Crohn’s dis- ease who had failed corticosteroids, immunomodulators, and anti-TNF therapy. These patients received 3 doses of FMT by nasojejunal infusion over 2 days with each dose consisting of 200 g of donor stools but none of the patients experienced clinical, biological, or endoscopic benefit 8 weeks later. More importantly, the fecal bacterial compo- sition of these 4 patients did not show clustering with their donors after FMT, unlike the cases in recurrent CDI. 10 Therefore, manipulating gut microbiome is a potential therapeutic target in the treatment of IBD, but the question remains why some individuals have dramatic improve- ments, whereas others do not following FMT. Herein, we present a case of induction of remission after a single FMT infusion in a patient with Crohn’s colitis who had failed immunosuppressive therapy. We further characterized fecal microbiota by performing 16S ribo- somal RNA pyrosequencing pre-FMT and post-FMT. CASE REPORT In August 2011, a 26-year-old man presented at his local emer- gency room (ER) with a perianal fistula. At that time, as he had no other gastrointestinal symptoms, the fistula was treated with fistulot- omy and antibiotics. The patient was well until April 2012, when he presented with another perianal fistula, again treated through fistu- lotomy and antibiotics. He was not referred to gastroenterology for further evaluation at that time, as there were still no reported changes in his bowel habits, which consisted of one formed bowel movement (BM) per day. In August 2012, he returned to the ER with a 1-month history of bloody diarrhea, abdominal pain, and a 10 lb weight loss. Before the fistulae, the patient had been healthy, not taking any medication. Laboratory investigation revealed Hgb level = 11.4 g/dL, mean corpuscular volume = 91 fL, white blood cell count = 14.8  10 9 /L, platelet count = 309 10 9 /L, C reactive protein (CRP) level = 24.8 mg/L, normal electrolytes, normal creatinine, and normal liver function test; stool was negative for culture and sensitivity (C&S), From the *Department of Medicine, University of Alberta, Edmonton, AB; and wDepartment of Environmental Science and Policy, George Mason University, Manassa, VA. Supported by grants from Alberta IBD Consortium; Alberta Innovates. D.K.: study concept and design; acquisition of data; analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content. N.H.: acquisition of data; analysis and interpretation of data; critical revision of the manuscript for important intellectual content. P.G.: analysis and interpretation of data; critical revision of the manu- script for important intellectual content; administrative, technical and material support. K.M.: study concept and design; analysis and interpretation of data; critical revision of the manuscript for important intellectual content; administrative, technical and mate- rial support. The authors declare that they have nothing to disclose. Reprints: Dina Kao, MD, FRCPC, Zeidler Ledcor Centre, 130 Uni- versity Campus, University of Alberta, Edmonton, AB, T6G2X8 (e-mail: dkao@ualberta.ca). Copyright r 2014 by Lippincott Williams & Wilkins CASE REPORT J Clin Gastroenterol  Volume 48, Number 7, August 2014 www.jcge.com | 625