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Invited Commentaries

Too Early to Determine Whether Fecal Microbiota Transplant has Therapeutic Promise for Ulcerative Colitis?

Russell, George H.

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Journal of Pediatric Gastroenterology and Nutrition: January 2015 - Volume 60 - Issue 1 - p 3
doi: 10.1097/MPG.0000000000000619
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See “Fecal Microbial Transplant Via Nasogastric Tube for Active Pediatric Ulcerative Colitis” by Suskind et al on page 27.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that can affect both children and adults. In UC, the gut bacterial ecosystem is typified by both a reduction in biodiversity and a loss of commensal flora such as Firmicutes and an increase in more proinflammatory Bacteroidetes species. Animal and human data suggest that dysbiosis may lead to immune dysregulation (1,2). Fecal microbiota transplant (FMT) is a novel therapeutic method by which stool is transferred from a screened, healthy donor to an individual with disease to modulate the gut bacterial ecosystem and theoretically promote health instead of uncontrolled inflammation.

The article by Suskind et al (3) in this issue of the Journal of Pediatric Gastroenterology and Nutrition is a pilot study of 4 individuals with moderate UC activity treated with a single FMT delivered by nasogastric tube after a short course of antibiotics, acid suppression, and bowel lavage. Although FMT was feasible and adverse events were mild and self-limited, FMT was not obviously effective in moderating UC disease as measured by the Pediatric Ulcerative Colitis Activity Index or by stool or serum inflammatory biomarkers. Moreover, 3 of 4 patients in the pilot study required progression to more aggressive standard medical management during 12 weeks of follow-up.

Anecdotal and prospective reports have shown that FMT is exceptionally promising in curing recurrent Clostridium difficile infection in approximately 90% of affected individuals. Anecdotal case reports of dramatic response of UC with FMT have been published, but only limited data from prospective clinical trials are yet available. In a similar pilot study of 10 pediatric patients using daily FMT by enema for 5 days, Kunde et al showed that approximately 70% of patients had clinical response when measured by Pediatric Ulcerative Colitis Activity Index that was maintained for up to 1 month (4). A prospective randomized placebo-controlled study of 53 adult patients with UC presented in an abstract form by Moayeddi et al suggests that repeated weekly FMT by enema during 3 to 4 months can induce remission in up to 33% of patients when measured by Mayo clinical scoring (5). Our group has shown that an upper gastrointestinal route of delivery is equally effective when compared with a colonoscopic delivery approach for patients with recurrent C difficile infection, restoring the lack of gut biodiversity seen after both infection and aggressive antibiotic treatments (6). It is possible that the same is not true for UC, and that Suskind et al may have found greater success in this pilot study by using an alternative FMT delivery method.

Both clinicians and patients anticipate FMT to be a potential therapeutic tool for UC with unbridled enthusiasm. The work of Suskind et al suggests that further studies are necessary. Research trials must more clearly establish clinical use, long-term safety, required dosing of donated stool, matching of donor to recipient, delivery method, duration of response, best time in disease course to use FMT, and nature of effect on the transplanted gut microbiota. Manipulation of the gut microbiota represents a new paradigm for advanced therapy of UC. There exists hope that this new therapy may ultimately spare many individuals from the need for immunosuppressive medications and biologic therapies; however, further studies on larger and well-defined UC populations are needed with a longer follow-up to establish the efficacy and long-term safety of this treatment.

REFERENCES

1. Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007; 104:13780–13785.
2. Papa E, Docktor M, Smillie C, et al. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. PLoS One 2012;7:e39242.
3. Suskind DL, Singh N, Nielson H, Wahbeh G. Fecal microbial transplant via nasogastric tube for active pediatric ulcerative colitis. J Pediatr Gastroenterol Nutr 2015; 60:27–29.
4. Kunde S, Pham A, Bonczyk S, et al. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr 2013; 56:597–601.
5. Moayeddi P, Surrette M, Wolfe M, et al. A randomized, placebo controlled trial of fecal microbiota therapy in active ulcerative colitis. Gastroenterology 2014; 146:s-159.
6. Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors—a randomized, open label, controlled pilot study. Clin Infect Dis 2014; 58:1515–1522.
© 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,