Fecal Microbial Transplant 101

reedus (37)in #health • 8 years ago (edited)

WHAT IS FECAL MICROBIAL TRANSPLANT?

Fecal microbiota transplantation simply involves taking fecal bacteria from a healthy individual, the donor, and implanting it into the recipient. The process is thought to bring about the restoration of a healthy gut microbiome.

But how is FMT administered?

The route of administration for transplant material varies between institutions, but it can be done transcolonoscopically, by enema, orogastric tube, and as of quite recently, in the form of a pill1. It is still being debated and researched which method(s) is most effective, and each has different characteristics. For example, enema administration is generally cheaper and safer, but colonoscopy allows for assessment of the mucosa and ruling out of other pathologies¹.

WHAT IS FMT USED FOR?

As of right now, the only treatment FMT is approved for by health Canada, is treatment of recurrent C. difficile infection that is not responding to conventional therapy. The conventional therapy is antibiotics. However, upon further consideration of C. difficile, this treatment can seem somewhat counterintuitive.

What is C. difficile?

C. difficile, or clostridium difficile is a antibiotic associated, spore-forming bacteria and opportunistic pathogen. It produces a toxin which causes infectious diarrhea and colits—termed clostridium difficile colitis. The incidence of C. difficile has been increasing, coinciding with the increased use of broad spectrum antibiotics. As diagrammed below, taking antibiotics is thought to disrupt the gut bacteria , which can increase the risk of C. difficile infecting and colonizing the gut.

So, antibiotics predispose a patient to C. difficile, and then upon being infected with C. difficile, more antibiotics (granted they may be more specific) are used to treat it. 20% of patients have recurrence, and the risk increases successively from there. As shown in the figure below, by the time of multiple C. difficile infections, the bacteria composition of the gut has changed significantly from the original healthy composition of bacteroidetes and firmicutes.

On the other hand, fecal microbiota transplant has reported success rates as high as 90%, and with a second transplant the rates approach 100%. This is miraculous and there are many who believe FMT should be used a first line treatment for C. difficile.

HOW DOES FMT WORK?

The mechanism responsible for FMT’s success is not fully understood. Ultimately, the donors’ fecal bacteria bring about the resolution of the patient’s dysbiotic microbiome to that of a healthy one. However it is not clear whether the patient’s original microbiome is being restored, or a combination of both the donor and recipient microbiome is. There is evidence for the latter as Fuentes et al., found that patients being treated with FMT acquire some signature species unique to the donor, and specific donors seem to have larger impacts on the recipients microbial composition than others².

But is it just the patient’s microbiome that is being restored by FMT?

Probably not! Studies have provided strong evidence that bile acid metabolism is also altered by FMT. The gut microbiota are involved in bile acid metabolism. Primary bile acids are produced by the liver and then metabolized in the intestine by bacteria to form secondary bile acids. It has been shown that C. difficile patients have high primary and low secondary bile acid concentrations in the gut, whereas donors and patients post FMT have the opposite³.

What do bile acids have to do with C. difficile? Primary bile acids germinate C. difficile, whereas secondary bile acids have been shown to inhibit its growth in vitro³. Therefore, curing of C. difficile infection by restoration of the gut microbiome by FMT may be mediated by this change in bile acid metabolism, perhaps providing an entirely new avenue of therapeutic development.

WHAT OTHER DISEASES CAN FMT POTENTIALLY TREAT

Since FMT seems to work by resolving the diversity of the patient’s microbiome (and the resulting metabolic changes this induces), it would seem logical that FMT would have applications in many other diseases. After all, a dysbiotic microbiome has been implicated in numerous health conditions, including obesity!

Indeed, although FMT is still only approved for non-responsive C. difficile, it has shown promise in other conditions. Dr. Kao was able to induce remission in a Crohn’s patient using a single transplant⁴. Typically however, ongoing fecal tranplants are needs with IBD to maintain remission. Dr. Kao also used FMT to treat a patient with mild hepatic encephalopathy, and achieved improvement in cognitive scores⁵. The improvement was dependent on recurring transplants however.

In addition, a doctor has observed that upon treating some patients with both CDI and Parkinson’s disease using FMT, the Parkinson’s symptoms began to disappear⁶.

The potential of FMT is also currently being explored in other conditions including various autoimmune disorders, neurological conditions, obesity, metabolic syndrome, diabetes, and multiple sclerosis.

OBSTACLES TO FMT

Unfortunately, even with the success of FMT, there are a number of barriers to it’s widespread implementation for CDI. For one, Health Canada regulations are strict. FMT is considered a “biologic drug”, and can’t be used outside of a clinical trial for anything other than CDI not responding to antibiotics. Also, stool must be in classical form, without a cryoprotectant.

Remarkably, there is a lack of public funding to support FMT, and physicians are not paid for the time they spend treating patients using fecal transplants.

Additionally, donors must be heavily screened and must meet certain requirements. There is a limited number of available donors at the University of Alberta.

Cartoon of the day:

References:

Borody, T. J., Paramsothy, S., Agrawal, G. (2013). Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future. Current Gastroenterology Reports 15(8): 337
Fuentes, S., Nood, E., Tims, S., et al. (2014). Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection. International Society for Microbial Ecology 8, 1621-1633.
Weingarden, A. R., Chen, C., Bobr, A., et al. (2014). Microbiota transplantation restores normal bile acid composition in recurrent Clostridium difficile infection. Am J Physiology Gastrointestinal and Liver Physiology 306(4): G310-G319.
Kao, D., Hotte, N., Gillevet, P., & Madsen, K. (2014). Fecal Microbiota Transplantation Inducing Remission in Crohn’s Colitis and the Associated Changes in Fecal Microbial Profile. Journal of Clinical Gastroenterology, 48(7), 625-628
Kao, D., Roach, B., Park, H., Hotte, N., Madsen, K., Bain, V., & Tandon, P. (2015). Fecal microbiota transplantation in the management of hepatic encephalopathy. Hepatology, 63(1), 339-340
Ananthaswamy, Anil (January 19, 2011). "Faecal transplant eases symptoms of Parkinson's". New Scientist.

*All other images, slides, and information used with the permission of Dr. Dina Kao