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The bottom line of faecal microbiota transplant… is it all its cracked up to be?

Alternately described as the “ultimate probiotic” or for the more squeamish, “a bit gross”, faecal microbiota transplants (FMT) have recently been getting plenty of media coverage. Hailed by some as a miracle cure for conditions as wide ranging as obesity, auto-immune conditions and bacterial infections, FMT treatment utilises donor faeces delivered via enema or colonoscopy to deliver a diverse and healthy gut bacterial make up (known as the microbiome) to the recipient. More and more patients are being offered the treatment, and stool banks are being set up in cities around the world. But is the hype justified?

 

A new use for an old treatment

 

FMT is a surprisingly old therapeutic approach to gastrointestinal dysfunction, with evidence of the Chinese medicine doctor Ge Hong administering human faecal suspension by mouth to treat food poisoning or severe diarrhoea in 4th century China. FMT as we know it today was first proposed in 1958 by Dr Ben Eiseman for the treatment of a gastrointestinal condition called pseudomembraneous colitis. Despite his success, the treatment had trouble taking off, perhaps in part due to its taboo-like nature. In addition, issues with regulation and licensing hampered its take up in the US. This began to change in 2013, when research was published in The New England Journal of Medicine, showing the astounding success of the use of FMT to treat Clostridium difficile infection (CDI). CDI most commonly occurs among hospital patients who have received antibiotics. Symptoms include severe and persistent diarrhoea, with up to 15,000 people dying from the infection each year in the US alone. Standard treatment at the time was vancomycin, which in many cases did not stop the infection at all. This study saw 94% of patients recovering after FMT, whereas less than 30% of patients given vancomycin recovered!

 

FMT is now being offered for CDI at several hospitals around the world. Currently, in hospitals where FMT is used, donor faeces are screened for things like infectious pathogens, gastrointestinal conditions, antibiotic and other medication use. Both fresh and frozen samples have been used, which are both mixed with saline and then strained to create a suspension. If the sample is frozen, glycerol is also added to protect microbial cells from damage caused by freezing. The mixture is then delivered via a colonoscopy or an enema.

 

 

 

Can we use FMT for more than just Clostridium difficile infections?

 

The 2013 CDI study really kick-started the current FMT boom. While this is currently the only condition approved for FMT treatment, there is some evidence it may be useful for treating other gastrointestinal conditions like Crohn’s disease. There are also a number of clinical trials happening now looking at FMT in conditions such as hepatic encephalopathy, multiple sclerosis, melanoma and ulcerative colitis. It is hoped that these trials will help us to further understand how FMT works, and where it would be the most useful. People are even trying DIY FMTs (although we would not recommend this)!

 

Here is a list of all current clinical trials registered in Australia, the USA/Canada and Europe using FMT. Keep in mind though, there are many more studies happening that are in their earlier stages and therefore not registered on these site. 

 

Donating poo, just like donating blood?

 

Businesses are taking advantage of this boom, with companies such as OpenBiome operating stool banks or go-betweens between donors and recipients. After extensive screening processes, in some cases donors are paid for their contributions, and donate regularly. In the future, stool banks would also make excellent repositories for research purposes.

 

Work is also being done looking at the difference between a traditional FMT and a pill version, where the faecal sample could be freeze-dried, concentrated and then processed into pill form. One study has shown that pill FMTs have similar success and safety rates in CDI to that via enema or colonoscopy. However, capsules contained frozen faecal material, which limits their transportability, and patients had to take 40 capsules, which would not be ideal in patients who are already taking other medications.  

 

So whats stopping us all getting FMTs?

 

While the enthusiasm for FMT is warranted, we still have a long way to go before we are successfully treating a range of conditions with FMT. Scientists have only scratched the surface of what there is to know about the microbiome. Therefore, we may need to be screening donors for even more things than we do currently. One example of this was shown when a woman received a faecal transplant from her obese daughter, and subsequently became obese herself, despite never previously having troubles with her weight. While this may indicate that our microbiome may have more power over us than we even know, there are lots of other reasons the woman may have put on weight. Obviously of course, the risk of transmissible diseases means our screening procedures need to be very stringent and careful.

Additionally, we haven’t worked out the best way to measure problems or adverse events associated with FMT. Luckily, very few negative symptoms have been reported so far. Lastly, the fact that we don’t know exactly why or how FMT works may be stopping us from designing the ideal protocol for maximum efficacy. Do we need a special diet after FMT to increase its viability? Do we need to store or culture the sample in a particular way? The only way to figure this out will be more well-designed clinical trials.

 

So while this is an exciting time in microbiome research, it might not quite be time to hinge our hopes on it being a cure-all just yet!

 

 

 

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