Microbiome medicine: “Unlocking” the secrets behind fecal transplant “super donors”

22 Jan 2019 --- Fecal transplants could be used to treat intestinal disorders such as inflammatory bowel disease, and perhaps even help prevent Alzheimer's and cancer, if the secrets of the gut-rejuvenating properties of “super donors” could be unlocked, say Australian researchers. The researchers reviewed fecal transplantation trials for clues to the origin of the “super-donor” phenomenon, yet concluded that further research is needed to uncover the role of external factors, such as diet and naturally occurring gut diversity.

The report, published in Frontiers in Cellular and Infection Microbiology, notes that “super donors” can provide the necessary bacteria to restore gut chemicals that are lacking in those suffering from illnesses such as irritable bowel disease (IBD) and diabetes. As Alzheimer's, multiple sclerosis, cancers, asthma, allergies and heart disease are all associated with changes to gut bacteria, understanding what makes a fecal “super donor” could make “poop the new panacea.”

“We see transplants from super donors achieve clinical remission rates of perhaps double the remaining average. Our hope is that if we can discover how this happens, then we can improve the success of fecal transplantation and even trial it for new microbiome-associated conditions,” says the senior author of the research, Dr. Justin O'Sullivan, from the University of Auckland.

“We know already that changes to the gut microbiome can contribute to disease, based on studies in germ-free mice as well as clinical improvement in human patients following restoration of the gut microbiome by transplanting stool from a healthy donor,” he adds.

While the overall cure rate for recurrent diarrheal infection exceeds 90 percent, trials of fecal transplantation for other conditions like inflammatory bowel disease exacerbations and Type 2 diabetes have had much more mixed results, averaging nearer 20 percent.

“The pattern of success in these trials demonstrates the existence of ‘super donors,’ whose stool is particularly likely to influence the host gut and to lead to clinical improvement,” explains O'Sullivan.

“Super donors”
The fecal transplants were reviewed for clues to the origin of the “super donor” phenomenon.

“It is well-known that responders typically exhibit a higher microbial diversity than non-responders. In line with these observations, a larger number of species in the donor stool has been shown to be one of the most significant factors influencing fecal transplantation outcome,” says O’Sullivan.

In particular, super donor stool tends to have high levels of specific “keystone species.” These are bacteria that produce chemicals, yet they often lack in the host gut and can contribute to disease.

The keystone species theory can be tested, of course, by selecting donor stool rich in particular strains – or by designing “precision” transplants with a defined mixture of beneficial bacteria, such as a probiotic.

The approach has been applied successfully to prevent complications in a small sample of patients with liver disease. However, this study showed that microbial enrichment in the donor does not completely guarantee enrichment in the recipient. Meaning, there must be more to “super donors” than keystone species.

The balance of other bacteria present, and the interactions between them, seems to influence the retention of keystone species. Yet, the researchers discovered that it matters not only which bacteria are present, but what is present in and around the bacteria.

“For example, the success of fecal transplants has been associated in some studies with the transfer of viruses which infect other gut microbes. Some cases of recurrent diarrheal infection have even been cured with transplants of filtered stool, that has had all the live bacteria filtered out but still contains DNA, viruses and other debris,” adds O’Sullivan.

Ultimately, O'Sullivan and colleagues acknowledge that super donors may not fully account for successful fecal transplantation.

Some fecal transplant failures may be attributable to the gut's immune response to transplanted microbes, he explains further. This could stem from an underlying genetic difference between the donor and the recipient.

“Supporting the transplanted microbiome through diet could also improve success. It has been shown that a rapid change in diet, such as a switch from an animal-based to an exclusively plant-based diet, can alter the composition of the gut microbiota within 24 hours.”

They recommend that future fecal transplant trials routinely record information on the genetic background and dietary intake of recipients so that we can better understand their impact on transplant engraftment and clinical remission.

Fecal metabolome
Last year, researchers at King’s College London, UK, also set out to dig deeper into the function of gut bacteria. The researchers have set out to create a database of fecal metabolites – compounds produced by the gut microbiome – in an attempt to shed light on the relationship between what we eat, the way it is processed by our gut microbes and how we accumulate abdominal fat. 

Within this research, the researchers found that the fecal metabolome is influenced mainly (80 percent of its variance) by environmental factors, among which are the gut microbial composition and a person’s diet. It is also strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity.

According to the researchers, fecal metabolic profiling is a promising tool to explore links among microbiome composition, host phenotypes and heritable complex traits.

“The fecal bacteria metabolome allows us to understand the function of different bacteria in the gut. It is not just important to know what bacteria are present in the gut, but also what these bacteria do,” study co-author Cristina Menni tells NutritionInsight.