What Makes a ‘Super’ Fecal Donor Could Be in Their Genetics, Diet

Fecal Microbiota Transplantation (FMT) success rates of the past have relied on the rationale “one stool fits all,” but that might not be the case.

Keystone species, host-genetics and diet may all play a role in “super donors”—who elevate FMT success rates, according to a new study published in Frontiers.

Fecal transplants in patients with Clostridium difficile infections, or diarrheal infections, show to have a 91 percent success rate with FMT, yet chronic conditions such as Alzheimer’s, multiple sclerosis, cancer, asthma, allergies and heart disease do not always have similar outcomes. (The fecal transplantation success rate for inflammatory bowel disease, or IBD, and type 2 diabetes is only 20 percent).

Even with varying FMT success rates for these chronic conditions, these “super donors” have paved the way by achieving a higher clinical remission rate.

In recent research, the microbiome has shown to largely influence disease and health. In this study, researchers suggested that the phenomenon of the “super donor” may be due to a diverse, large quantity of species in the donors’ microbiome—or keystone species.

These keystone species were revealed to be much higher in super donors and played a significant role in FMT success—but keystone species are not the only bacteria playing a role. The interaction between other bacteria with keystone species, including viruses, can affect overall FMT success.

“The success of fecal transplants have been associated in some studies with the transfer of viruses, which infect other gut microbes,” said Justin O’Sullivan, senior author of the paper, from the University of Auckland. “Some cases of recurrent diarrheal infection have been cured with transplants of filtered stool, that has had all the live bacteria filtered out, but still contains DNA, viruses and other debris.”

Bacteria has a heavy influence on disease because it produces chemicals in the gut that can fight disease. If the gut lacks this bacteria, it also lacks crucial chemicals and could lead to gut dysbiosis, or low microbial diversity, which is associated with many diseases. Butyrate, for example, is a chemical produced by gut bacteria. In recent studies, this chemical has been associated with prolonged clinical remission of IBD and diabetes. This chemical is known to regulate the immune system and energy metabolism.

What’s more, genetic differences between the patient and the donor may influence FMT outcomes. Genetics shape gut bacteria. Five to 10 percent of bacterial taxa variability can be explained by genetics alone. Genetic differences between donor and patient could influence transplant success because of the gut’s immune response to the microbes coming from the donor, underlying the importance of genetics in whether a transplant will be successful or not.

Another factor that influences FMT success rates and what makes a super donor: diet.

“Supporting the transplanted microbiome through diet could also improve success,” O’Sullivan said. “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.”

The researchers also found that stool donors who were rich in Clostridium cluster IV and XIVa (Ruminococcaceae and Lachnospiraceae family of bacteria) resulted in a positive response in IBD patients to FMT.

Keystone species, genetics and diet are what contribute to FMT success or failure, not just the phenomena of a super donor’s stool alone. By unraveling what makes a super donor, the proper screening can be conducted that helps understand the impact on patient remission—including screening for genetic background and dietary intake.