Eww! If the thought of gulping down helminth eggs in an effort to mitigate the symptoms of IBD, psoriasis and other autoimmune diseases wasn’t unpalatable enough, we now face the reality of having someone else’s faeces fertilizing our guts! Nevertheless, it appears that the incentive for using these types of ‘paleo’ therapeutic approaches is increasing, driven mainly by problems related to antimicrobial resistance, faltering immunological pathways and intestinal dysbiosis, all of which may be intrinsically linked. Meanwhile, authorities are struggling to develop regulations in the face of multiple trials supporting the efficacy of faecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infections (CDI).
A few weeks ago, @Liz_Atchley uttered on Twitter “If I'm ever in need of a fecal transplant, just let me die”. Same week, @beardbrain went ‘"There Is No ‘Healthy’ Microbiome". So don't get that fashionable fecal transplant unless you really need it!”’ The last tweet refers to an article that appeared in the New York Times.1 What the article actually said was that it appears that there is no single healthy microbiome, that the microbiome in each individual may undergo dynamic changes, and that perfectly healthy people may differ greatly in terms of microbiota structure and diversity. In fact, each of us appears to have a unique gut microbiome that may, however, be perturbed (e.g. by antimicrobials or certain types of diets), leading to disease, possibly including metabolic syndrome.
Meanwhile, there is solid scientific evidence that some patient groups, especially patients with recurrent CDI, benefit from FMT aiming to correct intestinal dysbiosis—microbiota alterations—by instilling fecal microorganisms from a healthy individual into the intestine of a patient. In the US, a total of 15%—20% of antibiotic-related cases of diarrhea and most cases of pseudomembranous colitis can be attributed to CDI, which is involved in three million cases of diarrhea and colitis per year, with many thousands succumbing to infection.2 Recurrence of CDI appears to be common, affecting around 15%—20% of cases. In their current CDI guidelines, The European Society for Clinical Microbiology and Infectious Diseases (ESCMID) recommends the use of FMT rather than vancomycin or fidaxomicin in patients who have experienced at least two CDI recurrences (i.e. three CDI episodes in a single patient).3,4
The EAGEN Gut Microbiota 2014 meeting took place in Rome in September, and some of the talks are now available in the UEG Education Library (please see below for the list of presentations). In one of the presentations, Dr Luca Pani from the Italian Medicines Agency not only ‘brutally’ explains the bread and butter of FMT and dishes out compelling facts on FMT success rates, but also expands on the vast potential applicability of FMT, which may prove valuable in preventing, mitigating, and/or treating complex disorders, such as multiple sclerosis, colorectal cancer, metabolic syndrome and disorders stemming from imbalances in the gut–brain axis.2
Moreover, Dr Pani importantly touches upon the intricate issues related to regulating FMT procedures, and asks several important questions. Should food and drug administrations control FMTs? Who are the FMT manufacturers? How about donor exclusions and testing of donor stool—which of the 40,000 species in stool should we allow to enter the recipient? Can single ‘active ingredients’ be identified or does the success of FMT rely on the combined actions/influence of diverse microbial communities?
There have been discussions about whether FMTs are in fact tissue transplants or medicines, and there is also a continuum of varieties of FMT, from the infusion of donor faeces screened for pathogens prior to administration, to cocktails of enteric bacteria specifically chosen for and selectively grown on agar plates. Are we talking full-spectrum microbiota or defined microbiota ecosystems? Instead of FMT, are we moving towards ‘Next-Generation Microbiota Therapeutics’5 such as ‘RePOOPulate’, a synthetic stool produced by a ‘Robogut’6? Apparently, FMT regulations vary from being very strict, such as those developed by the US FDA, to being more or less absent in most other countries. In Austria, FMT is regarded as a therapeutic intervention that is not to be considered a pharmaceutical drug and is therefore exempt from regulation by the Austrian Medicines Act.4
As Dr Pani explains, the statistics on FMT for successfully treating C. difficile infections are clear—no need for P values anymore.2 Success stories keep coming in, which will eventually make FMT more palatable to the general public, and so it probably won’t be long before FMT will be triaged by health care professionals, medical companies, and national FDA agencies. Efforts aiming to relax regulations and ensure standardization as much as possible will be crucial in order to reduce the incidence of DIY-related mishaps and to quickly gain more insight into the therapeutic potential of FMT.
Hungry for more? Then why not sit back and update yourself on FMT constituents, indications, feasibility, safety, practicality, and regulations, and—maybe first and foremost—examples of professional experience with FMT by having a look at the accepted articles section in Clinical Microbiology and Infection. I also recommend watching the talk on FMT and recurrent CDI by Lawrence Brandt given at the Gut Microbiota for Health 2nd World Summit.7
- Yong E. There Is No ‘Healthy’ Microbiome. The New York Times. November 1, 2014.
- Pani L. Microbial transplantation as a new therapy option in medicine: The views of the Italian Medicines Agency (AIFA). Opening lecture at EAGAN Gut Microbiota 2014.
- Debast SB, Bauer MP, Kuijper EJ, et al. European Society of Clinical Microbiology and Infectious Diseases: Update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect 2014; 20 (Suppl 2):1–26
- Kump PK, Krause R, Allerberger F, et al. Fecal microbiota transplantation—the Austrian approach. Clin Microbiol Infect Epub ahead of print 1 October 2014. DOI: 10.1111/1469-0691.12801
- Petrof EO and Khoruts A. From stool transplants to next-generation microbiota therapeutics. Gastroenterology 2014; 146; 1573–1582
- Petrof EO, Gloor GB, Vanner SJ, et al. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 2013; 1:3
- Brandt L. Fecal Transplantation for the treatment of Clostridium difficile infection. Presentation at the Gut Microbiota for Health 2nd World Summit Madrid 2013.
EAGEN Gut Microbiota 2014 Presentations
Further UEG Education Resources
Brandt LJ. American Journal of Gastroenterology Lecture: Intestinal microbiota and the role of fecal microbiota transplant (FMT) in treatment of C. difficile infection. Am J Gastroenterol 2013; 108: 177–185. DOI:10.1038/ajg.2012.450
Singh R, Nieuwdorp M, Ten Berge IJ, et al. The potential beneficial role of faecal microbiota transplantation in diseases other than Clostridium difficile infection. Clin Microbiol Infect Epub ahead of print 7 November 2014. DOI: 10.1111/1469-0691.12799.