Last updated February 15, 2018 at 2:33 pm
The success of faecal transplant therapy is determined in large part by similarities between donor and recipient microbial gut populations, research has found.
Despite the rapidly increasing popularity of faecal transplants for treating a range of diseases, a study led by Harvard geneticist Christopher Smillie is the first to identify the mechanisms by which the process works.
Faecal transplant pretty much involves what the term suggests. Poo from a healthy person is transferred in to the gut of an unhealthy recipient. The principle behind it is elegant, even if the practice itself is a little nauseating.
The average human gut contains trillions of bacteria which are collectively called the microbiota.
The microbes are responsible for digesting food and are also thought to play strong roles in conditioning host metabolism and the function of the immune system.
Treating Clostridium difficile
When the gut microbiota is damaged – commonly through the application of antibiotics – not only do these critical functions decline, but the door to opportunistic pathogens swings wide open.
This is particularly the case with Clostridium difficile, a gastroenterological disease that kills 30,000 people around the world every year. Poorly functioning microbiota is also thought to play a role in the development of several other conditions, including inflammatory bowel disease, metabolic syndrome and even autism.
Faecal transplant has been found to be a successful treatment for 85% of C.difficile cases, but, surprisingly, the mechanisms by which it works remain largely unknown.
This presents a considerable hurdle to advancing the therapy. There is a general (and quite reasonable) desire among researchers, clinician and, it can be imagined, patients for faecal transplant technology to become considerably less faecal.
If the donated gut microbiota could be transferred in, say, tablet form rather than as a stranger’s poo, the procedure could become rather more palatable. It would also become safer – despite protocols in place, there is always a risk of unforeseen infections associated with handling faeces.
Before pills can be formulated, however, it is necessary to know just how the transplanted microbes behave in their new home, and what factors influence whether they thrive or fail.
Highly individual factors
Smillie and his colleagues set out to determine whether success is governed by what might be called universal principles. These include the law of mass action: a simple rule found in chemistry that says the rate of a chemical reaction is directly proportional to the amount of stuff there is to react with.
Such simple interactions would effectively reduce the next-generation of faecal transplants to matters of bacterial population size and ratio – and make their design only a question of precision engineering
However, the researchers acknowledge, the success of a transplant may also be governed by highly individual factors – such as a patient’s genetics, diet, medication load, and immune health. If these factors are dominant, then identifying common links becomes much more difficult.
To make their findings, the scientists studied 19 C.difficile patients, all of whom received transplants from one of four donors. The microbiomes of the patients were tested before the procedure, and then again at intervals ranging between one day and four months. All up, the researchers note, they analysed 79 stool samples.
The results were complex – with bacteria picked up from the external environment joining the microbes present before and after transplant – but one clear mechanism emerged. The recipient, rather than the donor, exerts significant influence over which species and strains in the biota increase in numbers.
The researchers found that the microbial species in the donor poo that matched those already present in the recipient were most likely to thrive. “Host control, rather than dose dependence, determines bacterial abundances,” they conclude.
The Harvard team followed up its findings by performing similar tests on faecal transplant recipients who suffered from metabolic syndrome, and found similar results. While not conclusive, the data suggest that reactions to faecal transplants follow general principles that transcend individual patients or diseases.
In a paper published in the journal Cell Hose and Microbe, Smillie and his colleagues recommend further tests using the 145 faecal transplant clinical trials currently underway in the US.