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The human intestine contains at least 1014 bacteria, with hundreds to thousands of different species, which exist in harmony with their host. The role of this intestinal flora, or microbiota, in maintaining the health of an individual is increasingly being appreciated.
The composition of the microbiota is significantly affected by the use of antibiotics and certain diseases, causing microbial imbalances or “dysbiosis”. Fecal microbiota transplantation (FMT) is the transfer of fecal matter and its associated microbiome from a “healthy” individual to a recipient, to correct the dysbiosis and restore balance.
FMT is not a new concept, and its first mention in the literature was during the 4th century when Ge Hong described the use of fecal suspension by mouth for treatment of severe diarrhea or food poisoning.
The increasing interest in FMT again over the last several decades has to a certain extent paralleled the increasing prevalence of Clostridium difficile infection and the desire to find better treatment options for those suffering from severe or refractory infection.
Clostridium difficile infection is the leading cause of hospital-acquired diarrhea in the USA and can cause significant morbidity and even be life-threatening, with the Center for Disease Control and Prevention (CDC) reporting 14,000 Clostridium difficile related deaths each year.
It is associated with the use of antibiotics, which can lead to dysbiosis that predisposes the host to Clostridium difficile infection. The number of cases over the last 20 years has more than doubled with increasing severity and resistance to standard therapy.
Clostridium difficile infection is generally treated with antibiotics such as metronidazole and oral vancomycin, which are effective against the bacterium but do not address the underlying dysbiosis which predisposes to the condition. Therefore recurrence of Clostridium difficile infection is high, with up to a 10-20% recurrence rate after initial antibiotic therapy and up to 40-65% in patients who are retreated for a second episode.
FMT has been successfully used to treat recurrent Clostridium difficile infection, with the rationale that reintroduction of normal gut flora corrects the dysbiosis that can predispose to a recurrence of Clostridium difficile infection.
From combined analysis of all patient reports of FMT for recurrent Clostridium difficileinfection in the literature, the effectiveness for cure is over 90%. Moreover, the first randomized controlled trial for FMT for this purpose was published this year and showed that FMT was significantly more effective than a standard antibiotic course of vancomycin for the treatment of recurrent Clostridium difficile associated diarrhea.
If a person has had recurrent episodes of Clostridium difficile infection, despite treatment with traditional antibiotics, then they may be suitable for FMT. A fecal donor for the procedure is identified and screened carefully for infectious risks, much like a blood donor. The donor’s stool and blood are tested for specific infections that they could potentially pass on to the recipient.
At the time of the procedure, a fecal suspension is prepared and can be delivered to the recipient via the upper gastrointestinal tract, by nasogastric or nasoduodenal tube or via the lower gastrointestinal tract by colonoscopy or enema. Both routes are effective, however there is some suggestion in the medical literature that delivering the fecal material via the lower gastrointestinal tract may have an increased cure rate.
FMT appears to be safe, without major adverse effects or complications directly attributable to the procedure being published. Mild and transient adverse effects of abdominal cramping, gas and diarrhea have been reported following the procedure and are expected.
There is still concern about the potential of transmission of infectious agents through the stool, although this risk may be reduced by adequate screening of the donor.
Given the association of the intestinal microbiome with several conditions including autoimmune disease and obesity, there is a concern that transfer of fecal matter can inadvertently also transfer the propensity towards such disorders to the recipient. Long term follow-up studies are needed to investigate this potential risk.
FMT may also have a role in treatment of other disorders that are associated with altered intestinal microbiome. Currently preliminary investigation is being conducted into the role of FMT to treat inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and type 2 diabetes.
Biotech companies are also investigating creating and using “artificial feces” with bacterial colonies grown in a lab, to replace FMT. This would provide a safer and more standardized product than using human feces and is likely the way of the future. However, until this technology has been further developed and tested, FMT is currently the most effective treatment available for recurrent Clostridium difficile infection.