Scientists often seem to be looking for sacred chalices or real ammunition. But a group of microbiologists have now embarked on a more fragrant odyssey — one to find fantastical feces.
As data piles up on poop’s therapeutic potential, scientists have caught wind of the possibility that some of us are extraordinary excreters, dropping twos with divine healing powers. In a review article published on Monday 21 January in Frontiers in Cellular and Infection MicrobiologyUniversity of Auckland researchers are unearthing all the evidence for this deficient stool from the mountain of studies on fecal microbiota transplants, or FMTs.
An FMT is exactly what it sounds like: Stool containing gobs of gut microbes is dumped, injected, swallowed, or otherwise delivered into patients’ guts. The idea is that the relocated microbial communities will restore or replace the patient’s own gut inhabitants to improve health. After all, intestinal microbes can play a role in nutrition, metabolism, immune system function and infection protection. So patients with gut communities that are imbalanced and dysfunctional — aka dysbiotic — or who are overrun with pathogens will see health benefits from such gut build-up.
The most powerful evidence of the benefits of FMTs comes from studies in patients with: Clostridium difficile infections. usual, C. difference bacteria are kept in check by healthy gut communities. But when the opportunity arises, such as if someone takes antibiotics that curb their beneficial stomach bugs,C. difference can run amok and cause inflammation and diarrhea. And the infection can be difficult to squeeze. It is treated with more antibiotics, which only work about 80 percent of the time. The other 20 percent of patients will have recurrent infections. This is where FMTs pop in, essentially dirty bombing of the pathogens. A recent analysis of case studies and seven randomized trials found that FMT had a cure rate of approximately 92 percent in patients with relapsed C. difference infections.
But while FMTs have provided satisfying relief from: C. difference infections, scientists have endeavored to document such success in treating other conditions involving dysbiosis. These include everything from inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and allergic colitis to blood, liver, metabolic and neurological disorders. FMT could hypothetically help with these conditions. But of the few generally small trials to date, the results have been muddy. Some patients benefit from it, others do not.
However, a few interesting nuggets have emerged from the data. Scientists have been repeatedly hinted that supernatural poopers exist. The first whiff of evidence came in 2015 from a randomized clinical trial of FMT via enema to treat 75 patients with ulcerative colitis, a type of IBD. The FMTs beat placebo treatments but only had a 24 percent cure rate. However, when the researchers looked through the data, they found that seven of the nine patients who went into remission received stool from the same donor.
Researchers squeezed a similar finding from another randomized trial of FMTs for IBD treatment in 2017. In this case, researchers tried to pool fecal material from different donors to maximize the effects of each potent poop. Again, they only saw a 27 percent cure rate. But when they delved into the data, they found that pools of feces from a particular donor were far more likely to cure patients than any of the other dirty medleys.
Thus loo lore was born. “The term ‘super donor’ has been proposed to describe donors whose stools result in significantly more successful FMT results than the stools of other donors,” the Auckland researchers write.
Other FMT studies, including one involving patients with metabolic disorders, have dropped similar hints of super donors. But researchers are still not sure how to fish them out. Attempts to use stool microbial makeup — that is, overall bacterial diversity and relative abundance of specific species — have failed to reliably select superpoopers, the authors report. (Standard methods of screening FMT stool donors generally involve not harboring pathogens and being able to assess bacterial diversity.)
The authors point out that a range of other factors may be critical in determining the success of an FMT. For example, an FMT receiver’s own genetics may play a role. Likewise, a recipient’s native microbes and immune responses have the potential to wipe out transplanted entrants. And the recipient’s diet and medications — especially subsequent antibiotic use — can affect FMT results.
But other studies have shown that bacteria may not even be the key to the benefits of FMTs. A small study of five patients with C. difference infections found that only fecal filtrates could cure the infections. The filtrates do not contain bacteria or even the useful small molecules that make them. The filtrates contain only bacterial waste, proteins, DNA, antimicrobial compounds, metabolites and viruses, the Auckland researchers note.
“As more FMT-related clinical and microbial data are generated, it becomes clear that ‘one stool is not right for everyone’ in the context of treating chronic diseases with microbial dysbiosis,” the authors conclude.
Still, they write, “the donor plays an influential role in FMT results,” and the search for super donors is noble. “Further characterization of superdonors is likely to result in the development of more refined FMT formulations to standardize therapy and reduce variability in patient response.”
Frontiers in Cellular and Infection Microbiology2018. DOI: 10.3389/fcimb.2019.00002 (About DOIs).