Fecal Microbiota Transplants
Fecal microbiota transplants, or FMT, is the transfer of fecal material from one person to another, with the intent of replacing or augmenting the intestinal microbiota of the recipient with that of the host. It can be delivered from either end of the GI tract (via a colonoscopy or enema, or via a naso-gastric tube, although scientists have also found success using oral capsules). Presumably the donor is healthy and the recipient is suffering from some disease (but not always).
FMT has recently gotten a lot of attention, because it has been found to be (by far) the best available treatment for a life-threatening overgrowth of the colon by the bacterium Clostridium difficile. Even when it isn't fatal, C. difficile colitis is debilitating, with frequent bouts of explosive, bloody diarrhea. The disease most often starts after someone has received multiple courses of antibiotics over a relatively short time period to deal with some other infection; consequently, their native gut microbiota is greatly depleted and altered. Because C. difficile is resistant to many antibiotics, and it grows quickly in a microbe-poor, resource-rich gut environment, it can take over and begin secreting a toxin that, in extreme cases, literally kills the large intestine. The concentration of inpatients taking multiple antibiotics, and the difficulty of killing C. difficile spores on surfaces, have resulted in outbreaks of the disease in hospitals, nursing homes, and long term care facilities. Strict infection control procedures are essential in containing such outbreaks. Sometimes, however, cases of C. difficile colitis are 'community acquired', meaning that they occur in people who are living independently and who did not recently spend time in such institutions.
Ironically, until recently, the standard treatment for C. difficile colitis has been to use more antibiotics, usually vancomycin and/or metronidazole. While sometimes successful in eliminating the acute disease, antibiotic treatment also has a high rate of relapse, because the native microbiota continues to be disturbed, and C. difficile is not always completely eliminated. (Or C. difficile is reintroduced to the patient.) However, it has long been realized that C. difficile almost never becomes abundant or causes disease when it manages to colonize people with an intact, healthy microbiota. Consequently, some physicians began treating C. difficile patients with FMT, with much better results than vancomycin or metronidazole. Obviously, many diseases could also be transmitted via FMT, so the donor stool should be screened for known pathogens, and a donor has usually been sought among those close to the patient (e.g. spouse, sibling) to minimize the risk of introducing a new pathogen. While the Borody group has been publishing successful treatment results for decades (and the treatment itself is certainly much older), only in the last few years has awareness of FMT really taken off in the United States.
The FDA controversially announced plans in May, 2013 to regulate FMT as an experimental procedure which would have greatly curtailed its availability; after an outcry from patients and physicians the FDA reconsidered its decision.
The success of FMT in treating C. difficile colitis has led to attempts to use FMT for other diseases known to be (or thought to be) related to an abnormal composition of the gut microbiota, most notably ulcerative colitis. However, results thus far have been mixed, with none as dramatic as with C. difficile colitis. Differences in the treatment protocols may contribute to the mixed results, meaning that further research could improve the efficacy of treatment. However, infection with C. difficile is not as biologically complex as ulcerative colitis, Crohn's disease, and a number of other conditions where the gut microbiota are involved. (These other conditions are not thought to be due to a single pathogen, and the symptoms probably involve feedback loops between the gut microbiota and human physiology rather than being caused by a bacterial toxin.) Hence, there are reasons to think that FMT alone may not provide a cure for these conditions, even if it proves to be beneficial in some cases.
October 2014 Update: A just-published study, based on experiments only in mice (but including correlative data from humans) has identified one bacterial strain, and more importantly a biochemical mechanism, which contributes to the ability of the native microbiota to resist overgrowth by C. difficile. (See Buffie et al. in the scientific literature below.) The study doesn't show that this mechanism is the only cause of the resistance to C. difficile in intact gut communities (although it might be), but it does take us closer to having a probiotic strain or a pharmaceutical drug that prevents or cures C. difficile colitis after antibiotic treatment. This raises the question whether FMT might provide additional benefits (by quickly reconstituting something like an intact microbiome) that would not be obtained via a single-strain probiotic treatment. If so, that might still be an argument in favor of FMT, to balance against the undoubtedly greater risk of FMT using complex, incompletely-defined donor material. I'm not aware of any data addressing this question directly. There are two other approaches being taken to reducing the risk of FMT: the use of standardized donor material (Hamilton et al. below), and the use of multi-strain defined communities (essentially, a complex probiotic of native gut microbes, see Petrof et al. below).
FMT has recently gotten a lot of attention, because it has been found to be (by far) the best available treatment for a life-threatening overgrowth of the colon by the bacterium Clostridium difficile. Even when it isn't fatal, C. difficile colitis is debilitating, with frequent bouts of explosive, bloody diarrhea. The disease most often starts after someone has received multiple courses of antibiotics over a relatively short time period to deal with some other infection; consequently, their native gut microbiota is greatly depleted and altered. Because C. difficile is resistant to many antibiotics, and it grows quickly in a microbe-poor, resource-rich gut environment, it can take over and begin secreting a toxin that, in extreme cases, literally kills the large intestine. The concentration of inpatients taking multiple antibiotics, and the difficulty of killing C. difficile spores on surfaces, have resulted in outbreaks of the disease in hospitals, nursing homes, and long term care facilities. Strict infection control procedures are essential in containing such outbreaks. Sometimes, however, cases of C. difficile colitis are 'community acquired', meaning that they occur in people who are living independently and who did not recently spend time in such institutions.
Ironically, until recently, the standard treatment for C. difficile colitis has been to use more antibiotics, usually vancomycin and/or metronidazole. While sometimes successful in eliminating the acute disease, antibiotic treatment also has a high rate of relapse, because the native microbiota continues to be disturbed, and C. difficile is not always completely eliminated. (Or C. difficile is reintroduced to the patient.) However, it has long been realized that C. difficile almost never becomes abundant or causes disease when it manages to colonize people with an intact, healthy microbiota. Consequently, some physicians began treating C. difficile patients with FMT, with much better results than vancomycin or metronidazole. Obviously, many diseases could also be transmitted via FMT, so the donor stool should be screened for known pathogens, and a donor has usually been sought among those close to the patient (e.g. spouse, sibling) to minimize the risk of introducing a new pathogen. While the Borody group has been publishing successful treatment results for decades (and the treatment itself is certainly much older), only in the last few years has awareness of FMT really taken off in the United States.
The FDA controversially announced plans in May, 2013 to regulate FMT as an experimental procedure which would have greatly curtailed its availability; after an outcry from patients and physicians the FDA reconsidered its decision.
The success of FMT in treating C. difficile colitis has led to attempts to use FMT for other diseases known to be (or thought to be) related to an abnormal composition of the gut microbiota, most notably ulcerative colitis. However, results thus far have been mixed, with none as dramatic as with C. difficile colitis. Differences in the treatment protocols may contribute to the mixed results, meaning that further research could improve the efficacy of treatment. However, infection with C. difficile is not as biologically complex as ulcerative colitis, Crohn's disease, and a number of other conditions where the gut microbiota are involved. (These other conditions are not thought to be due to a single pathogen, and the symptoms probably involve feedback loops between the gut microbiota and human physiology rather than being caused by a bacterial toxin.) Hence, there are reasons to think that FMT alone may not provide a cure for these conditions, even if it proves to be beneficial in some cases.
October 2014 Update: A just-published study, based on experiments only in mice (but including correlative data from humans) has identified one bacterial strain, and more importantly a biochemical mechanism, which contributes to the ability of the native microbiota to resist overgrowth by C. difficile. (See Buffie et al. in the scientific literature below.) The study doesn't show that this mechanism is the only cause of the resistance to C. difficile in intact gut communities (although it might be), but it does take us closer to having a probiotic strain or a pharmaceutical drug that prevents or cures C. difficile colitis after antibiotic treatment. This raises the question whether FMT might provide additional benefits (by quickly reconstituting something like an intact microbiome) that would not be obtained via a single-strain probiotic treatment. If so, that might still be an argument in favor of FMT, to balance against the undoubtedly greater risk of FMT using complex, incompletely-defined donor material. I'm not aware of any data addressing this question directly. There are two other approaches being taken to reducing the risk of FMT: the use of standardized donor material (Hamilton et al. below), and the use of multi-strain defined communities (essentially, a complex probiotic of native gut microbes, see Petrof et al. below).
Selected Scientific Literature
Sofi et al., 2013: A recent systematic review of the literature for FMT treatment of C. difficile colitis. (abstract only)
Aroniadis and Brandt, 2014: Review of FMT by one of the leading practitioners in the U.S. (full text)
Kelly et al., 2014: Report of FMT success for C. difficile infection in immunocompromised patients. (abstract only)
Moayyedi et al., 2014: Statement of the Canadian Association of Gastroenterology on FMT for C. difficile and other conditions. (full text)
Buffie et al., 2014: Report of a single strain, Clostridium scindens, and a biochemical mechanism of bile acid transformation, that can confer resistance to C. difficile overgrowth. (abstract only)
Hamilton et al., 2012: Use of standardized, frozen, pre-screened donor material for FMT.
Petrof et al., 2013: Transplant therapy with a complex but known mixture of strains, as a substitute for actual FMT.
Aroniadis and Brandt, 2014: Review of FMT by one of the leading practitioners in the U.S. (full text)
Kelly et al., 2014: Report of FMT success for C. difficile infection in immunocompromised patients. (abstract only)
Moayyedi et al., 2014: Statement of the Canadian Association of Gastroenterology on FMT for C. difficile and other conditions. (full text)
Buffie et al., 2014: Report of a single strain, Clostridium scindens, and a biochemical mechanism of bile acid transformation, that can confer resistance to C. difficile overgrowth. (abstract only)
Hamilton et al., 2012: Use of standardized, frozen, pre-screened donor material for FMT.
Petrof et al., 2013: Transplant therapy with a complex but known mixture of strains, as a substitute for actual FMT.