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Conventional Medicine vs. Alternative Medicine and the FDA
An advantage of conventional medicine is its consistency. Conventional docs generally follow professional society recommendations, and have a similar standard of care, which values the known over the unknown. At least in theory, they use therapies whose risks and benefits have been evaluated. The drawback of this approach is that many patients have a medical aesthetic which favors the potential benefits (and concomitant risks) of therapies that have not yet been examined in trials, and MDs often won't consider discussing those therapies since they can't weigh the risks and benefits in the same way, and they could be legally responsible if a patient suffers an adverse event from an untested therapy.21
People often come to naturopathic doctors because the bedrock of our therapeutic armamentarium is made up of interventions that have not been evaluated using rigorous science. We use herbs, diet, exercise, hydrotherapy, and other traditional interventions and are comfortable operating outside the known evidence base.
With that in mind, I spent 2 years using FMT to treat patients with a variety of conditions before a letter from the American Gastroenterological Association to the FDA prompted the FDA to classify FMT as a drug and a biological agent.22 In April 2013 the FDA limited the use of FMT to clinical trials, but after objection from clinicians around the country who were seeing FMT save the lives of their refractory CDI patients, the FDA agreed to provide discretionary enforcement for clinicians preparing and administering FMT to treat refractory CDI.23 Many of my patients with IBD are determined to do home FMT, so I counsel them in what I believe to be best practice, in the interest of harm reduction and with hope for benefit. I believe that some of my patients still have their colons because of their use of home FMT.
The Fecal Transplant Foundation (whose board of directors I'm honored to serve on) now lists over 75 practices or physicians in the US offering FMT for patients with refractory CDI, including the Mayo and Cleveland Clinics.24
Safety and Efficacy
Clinicians who use FMT have had a growing sense for years now that FMT is very safe in the short term, massively effective for CDI, and perhaps helpful for IBD, IBS, and more.
Is it really effective? The one randomized, controlled trial published so far weighed a standard treatment for recurrent CDI (500 mg vancomycin 4×/d for 14 days) vs. an abbreviated course (500 mg vancomycin 4×/d for 4 or 5 days) followed by FMT nasoduodenal administration.25 They unblinded the study halfway through, and had to stop the study because the difference in the groups was so dramatic – only 25% of the treatment-as-usual group was cured, while all but 1 of the 16 FMT patients (94%) were cured after no more than two FMT infusions. This small study supports the 92% cure rate generally reported in case series.
Case series have indicated enough benefit for IBD13,14 that randomized controlled trials are warranted – at the time of this writing, 14 of the 35 FMT trials listed on clinicaltrials.gov are studying FMT for IBD.
Occasionally fascinating cases pop up, such as Borody's patient with Parkinson's whose symptoms completely resolved after FMT.26 Borody also reports a case of idiopathic thrombocytopenic purpura (an autoimmune condition) that resolved after FMT, and he reports three people with diagnoses of multiple sclerosis (MS) whose symptoms reversed after FMT, including one who had an indwelling catheter and was confined to a wheelchair, who then regained the ability to walk and urinate unassisted.27,28
I've used FMT with two patients with multiple sclerosis. They were both early in their diagnoses, and hadn't progressed very much. Following a series of FMT retention enemas, they remained quite stable, and one reported a side benefit. A type 1 diabetic for 20 years, he reported a distinct 20% to 30% drop in his postprandial insulin needs after FMT. He recently told me that at his last appointment, his neurologist told him "You have the brain of a healthy person." "Like a healthy person with MS?" he asked. "No," said the neurologist, "like a healthy person." It is important to note that he had also made dietary changes and undergone chelation and other interventions.
Is it really safe? There are still no serious adverse events clearly attributed to FMT, although there was a report of a 1-year-old with UC who had self-resolving ananaphylactoid responses to two out of seven FMT infusions. The infusions appeared to put her colitis into remission.29 There have been minor adverse events in my practice and the literature, such as gas, cramping, stool changes, increased flatulence, and borborygmi. In the short term it appears quite safe. One of my colleagues in the Fecal Transplant Foundation, gastroenterologist Colleen Kelly, is spearheading a plan to institute an FMT patient registry, where people will be able to report beneficial and adverse effects for years and decades after receiving FMT – that kind of data gathering might reveal long-term sequelae that we hadn't anticipated.
Are capsules safe? As of this writing I've administered FMT capsules (spun down at about 5000 G in a centrifuge) to eight patients with CDI, seven of whom have been quickly cured. Many people have asked about the safety of upper GI FMT, concerned that it could bring on small intestine bacterial overgrowth. Before I started administering capsules, I was relieved to see a Dutch group who'd given FMT to CDI patients through a duodenal tube; they biopsied the duodenum before FMT and 6 weeks afterwards, and did not find any difference in small intestine bacterial abundances before or after FMT.30
The Future …
Several groups are working to culture groups of fecal-derived microflora, lyophilize them, and encapsulate them. There is likely to be an FDA-approved lab-grown microbial product to treat CDI sometime in the next few years. Will those products be useful to treat IBD or other indications? Will other products be developed to treat those conditions? The products may be expensive, and perhaps limited in use (since they are extracts, not whole stool).
Other groups, including my own practice in Portland, are spinning their fecal slurries in large centrifuges, collecting the bacterial pellet, and triple encapsulating the whole-stool extract.
There will always be patients who want to try home FMT, and clinicians will serve their patients well by being knowledgeable about FMT best practice. In my practice, I'll continue to prepare FMT enemas and capsules for my refractory CDI patients. I'll continue to guide patients with IBD and other conditions in home FMT, and I'll continue to observe and collect data. I'm excited to see the science of microbial medicine grow, and happy to be one clinician quietly feeding its growth.
Notes
1. Borody TJ, Warren EF, Leis S, et al. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. 2003;37(1):42–47.
2. Borody TJ, George L, Andrews PJ, et al. Bowel flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med J Aust. 1989;150:604.
3. Bakken JC et al. for the Fecal Microbiota Transplantation Workgroup. Treating Clostridium difficile infection with fecal microbiota transplantation. Clin Gastroenterol Hepatol. 2011;9:1044–1049.
4. Zhang F, Luo W, Shi Y, et al. Should we standardize the 1,700-year old fecal microbiota transplantation? Am J Gastroenterol. 2012;107:1755.
5. Ibid.
6. Lehrer S. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2144.
7. Lewis A. Merde: Excursions in Scientific, Cultural, and Socio-Historical Coprology. New York: Random House; 1999.
8. Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44:854–859.
9. Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet. 1989;1:164.
10. Austin M, Mellow M, Tierney WM. Fecal microbiota transplantation in the treatment of Clostridium difficile infections. Am J Med. 2014 Jun;127(6):479–483.
11. Walia R, Kunde S, Mahajan L. Fecal microbiota transplantation in the treatment of refractory Clostridium difficile infection in children: an update. Curr Opin Pediatr. Epub 2014 Jul 18.
12. Kelly CR et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol. 2014 Jul;109(7):1065–1071.
13. Kunde S et al. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):597–601.
14. Allegretti JR, Hamilton MJ. Restoring the gut microbiome for the treatment of inflammatory bowel diseases. World J Gastroenterol. 2014 Apr 7;20(13):3468–3474
15. Grehan MJ et al. Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol. 2010 Sep;44(8):551–561.
16. Cao Y, Shen J, Ran ZH. Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: a meta-analysis and systematic review of the literature. Gastroenterol Res Pract. 2014;2014:872725.
17. Kahn SA, Gorawara-Bhat R, Rubin DT. Fecal bacteriotherapy for ulcerative colitis: patients are ready, are we? Inflamm Bowel Dis. 2012 Apr;18(4):676–684.
18. Davis, M. Fecal microbiota transplantation for ulcerative colitis [online article]. ND News and Review. Jan 2012. http://ndnr.com/gastrointestinal/fecal-microbiota-transplantation-for-ulcerative-colitis. Accessed Aug 16 2014.
19. Davis M. Fecal transplants in ulcerative colitis. Nat Med J. October 2013;(5)10.
20. Davis M. Fecal microbiota transplantation [audio recording]. American Association of Naturopathic Physicians conference. Keystone, CO; July 10–13, 2013. Available at http://backcountryrecording.com/collections/american-association-of-naturopathic-physicians-conference-2013/products/16-fecal-microbiota-transplantation-by-mark-davis.
21. Groopman J, Hartxband P. Your Medical Mind: How to Decide What Is Right for You. Penguin; 2012.
22. Letter from FDA to American Gastronomical Association et al. April 25, 2013. Accessed Aug. 15, 2014. Available at http://highroadsolution.com/file_upload_2/files/fda+response+letter+to+fmt+inquiry.pdf.
23. Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies. FDA website, accessed on 8/15/14: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/
Guidances/Vaccines/ucm361379.htm
24. Providers and trials [Web page]. Fecal Transplant Foundation. Accessed Aug. 15, 2014. http://thefecaltransplantfoundation.org/providers-trials.
25. Van Nood E et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407–415.
26. Guseo A. The Parkinson puzzle. [In Hungarian]. Orv Hetil. 2012 Dec 30;153(52):2060–2069.
27. Borody TJ, Campbell J, Torres M, et al. Reversal of idiopathic thrombocytopenia purpura (ITP) with fecal microbiota transplantation (FMT). Am J Gastroenterol. 2011;106:S352.
28. Borody TJ, Leis S, Campbell J, et al. Fecal microbiota transplantation (FMT) in multiple sclerosis (MS). Am J Gastroenterol. 2011;106:S352.
29. Vandenplas Y et al. Fecal microbial transplantation in a one-year-old girl with early onset colitis – caution advised. J Pediatr Gastroenterol Nutr. 2014 Jan 2.
30. Vrieze A et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012 Oct;143(4):913–6.e7.
 Mark Davis, ND, is the medical director of Good Life Medicine Center, an integrative medicine center in Portland, Oregon. His naturopathic practice, Bright Medicine Clinic, focuses on gastroenterological health. Dr. Davis is one of a handful of physicians in North America with clinical expertise in fecal microbiota transplantation (FMT), which he offers via retention enema and capsule.
Dr. Davis sits on the board of directors of the Fecal Transplant Foundation and is on the editorial board of the Natural Medicine Journal. He received his ND with honors in research from the National College of Natural Medicine.
You can find more information about Dr. Davis's practice and FMT at brightmedicineclinic.com
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