Recurrent Clostridium difficile colitis: the only validated indication
Currently, fecal microbiota transplant (FMT) is only indicated for the treatment of recurrent Clostridium difficile infections, but its indications might soon include other diseases where the involvement of the gut microbiota has been confirmed.
Recurrent Clostridium difficile colitis is the first cause of treatment-related diarrhea and affected over 450,000 Americans in 2011, of which 30,000 died. In France, 1800 deaths were associated to C. difficile infection in 20142. An estimated 5% of overall mortality in hospitalized patients is attributable to this bacterial strain.
Until the 1990s, C. difficile colitis was a relatively rare infection which was not considered a health hazard: an antibiotic treatment was enough to get rid of it. But in a 20-year period, the frequency of this disease more than doubled, while the efficacy of the antibiotics therapy dropped to a 20-30% success rate8,9. The bacterium is becoming increasingly resistant to antibiotics. It was not until the start of the 2000s and the sequencing of C. difficile genome when a particularly virulent strain was identified. It is resistant to antibiotics and able to produce 10 times the amount of toxins usually secreted by this bacterium.
Beware of relapse with repeated antibiotic courses!
Infection generally occurs after the destruction of the gut microbiota by repeated courses of antibiotics. C. difficile, which is present as resting spores in the colon, proliferates and changes to produce toxins that cause inflammation and diarrhea. Paradoxically, this infection is treated with antibiotics, which progressively exacerbate the gut microbiota disruption at each additional treatment course3 thus leading to a 35% rate of relapse2.
FMT should be preferred to antibiotics for recurrent cases
In 1958, the surgeon Ben Eiseman published 4 cases of pseudomembranous colitis that were cured with FMT and sparked interest in this method. Several articles described its efficacy to treat the recurrent form of this disease. But the true turning point came in 2013 with the publication of the first clinical trial in humans. This trial was designed with a robust methodology and demonstrated the therapeutic superiority of FMT over antibiotic therapy to treat recurrent and drugresistant forms of C. difficile infections.
INTERNATIONAL RECOMMENDATIONS FOR THE TREATMENT OF C. DIFFICILE INFECTIONS
Following the publication of the Dutch study, the European Society of Clinical Microbiology and Infection (ESCMID)10 updated its recommendations and included FMT as a possible treatment for recurrent C. difficile infection.
An isolated severe episode or a first colitis relapse must be treated with oral antibiotics.
Only the second relapse, which characterizes recurrent C. difficile colitis, warrants the use of a stool transplant.
2 Lagier JC, Raoult D. Fecal microbiota transplantation: indications and perspectives. Med Sci (Paris). 2016 Nov
3 Khoruts A, Sadowski MJ. Understanding the mechanisms of faecal microbiota transplantation. Nat Rev Gastroenterol Hepatol. 2016 Sep;13(9):508-16. doi: 10.1038/nrgastro.2016.98
8 Moayyedi P, et al. Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials. Med J Aust. 2017
9 Wortelboer K, et al. Fecal microbiota transplantation beyond Clostridioides difficile infections. EBioMedicine. 2019 Jun.