4 WORLD GASTROENTEROLOGY NEWS JULY 2014 Editorial | Expert Point of View | WDHD News | WGO & WGOF News | WGO Global Guidelines | Calendar of Events Is Fecal Microbiota Transplantation Through the Mid-Gut a Rescue Therapy for Refractory IBD? Faming Zhang, MD, PhD Associate Professor of Gastroenterology The Second Affiliated Hospital of Nanjing Medical University Nanjing, China Introduction The concept of using stool or extrac-tion from fermented stool from a healthy donor to treat patients with gastrointestinal diseases actually dates back to ancient China 1700 years ago, when the stool mat-ter was given orally to treat food poisoning and diarrheal diseases1. In 1958, stool from the healthy donor was given by enema to treat four patients with pseudomembranous colitis, which was the first record in English literature2. In recent years, fecal microbiota transplantation/ transplant (FMT) using frozen fecal microbiota has been proven as ef-fective with fresh feces for recurrent Clostridium difficile infection (CDI)3. As a milestone in the history of using gut bacteria to treat diseases, FMT was for the first time classified as a guideline-proposed option for treat-ing recurrent CDI in 20134. How-ever, the therapeutic power of FMT may be not only for CDI. Increasing evidence has indicated the potential role of FMT to treat inflammatory bowel disease (IBD)5, 6, although the reports of application of FMT to the management of severe IBD, especial-ly for CD, have been very limited in the literature7-9. We have initiated an exploratory study to answer whether FMT could be a safe and effective rescue therapy for refractory IBD. Method and Results Since October 2012, we have performed FMT in more than 130 patients with refractory severe IBD (without CDI) under two registered clinical trials. We treated selected patients who had failed or were not suitable for biotherapeutics, immuno-suppressant5, steroids, aminosalicylic acid, and even surgery. At least one week prior to FMT, all treatments were discontinued including biothera-peutics, immunosuppressant, steroids, and traditional Chinese medicine. One hour before FMT, intravenous injection of proton pump inhibi-tors and intramuscular injection of metoclopramide were given. The stool suspension was infused into the mid-gut by gastroscope under anesthesia, nasojejunal tube or tube via stoma. Therefore, the route of transplanta-tion was called mid-gut instead of duodenum. For some patients, mid-gut administration may be better than that through the colon. For example, in some patients with severe UC the colon cannot hold the contents in-fused by colonoscopy. In others with CD, strictures may limit the colonos-copy and there is a risk of perforation. A single FMT through the mid-gut with a stable volume of purified fecal microbiota is adequate for most of the refractory cases. A second FMT is done one week later for the very few patients who were steroid dependent and failed to respond to the first FMT. Otherwise, no more FMTs were necessary within a short period after the first FMT. The overall rate of clinical improve-ment and clinical remission based on the clinical activity in the first month was over 80% and 70%, respectively, which were higher than other as-sessment points within a 15-month follow-up. The body weight of pa-tients increased after FMT, and lipid profile improved as well. IBD related extraintestinal manifestations such as skin lesions also improved. FMT was a fast and significant effect in relieving Crohn’s colitis related abdominal pain. We have reported a case of severe re-fractory CD complicated with fistula and a large inflammatory mass that resolved after a single FMT as a res-cue9. This patient has had a sustained clinical, endoscopic remission for 18 months to date. The improved inflam-matory and immunological markers suggest the successful remodeling of the gut microbiome and maintenance of immune homeostasis. There have been no severe adverse events during endoscopic infusion or during the follow-up after FMT. We established a standardized laboratory protocol and clinical work flow, including donor identification, purification of fecal microbiota, banking of frozen fecal microbiota, endoscopic infusion procedure and a clinical evaluation system. The “shotgun” sequencing in-dicates that the crudely purified fecal microbiota should be quite similar to original feces. The standardized fecal microbiota preparation and clinical flow significantly simplified the FMT.
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