Not all poop is created equal, and 'super-poopers' could be life savers

It's a dirty job, but scientists around the world are eagerly jumping into research on poop.  

They're studying feces, collecting feces, analyzing feces, breaking it down, and even growing and cultivating it because they've recognized its tremendous value. The rich diversity of microbial life it contains could hold the key to treating a wide range of diseases, from chronic diarrheal disease to diabetes — even psychological disorders and cancer.

And the latest discovery they've made in clinical trials is that for reasons that are not yet clear, poop from some donors is much more effective in treating illness. This realization could help researchers take the next step in poop-based therapies for a large range of diseases. 

At the root of this research is the medical practice of fecal transplantation. For about a decade doctors have been using fecal transplants as a last-ditch treatment for antibiotic-resistant superbug gut infections. The most common target is C. difficile, which causes chronic and potentially lethal diarrheal infections. C. difficile typically causes problems after a patient has had antibiotic treatments that have wiped out most of the other microbes in their gut.  

A fecal transplant seems to work by repopulating the gut with its missing microbes, which can then displace and outcompete the troublesome C. difficile microbes. 

"It has a cure rate higher than 92 per cent, which is amazing for C. difficile, and it works within a couple of hours," Justin O'Sullivan, a molecular biologist from the University of Auckland in New Zealand, told Quirks & Quarks' Bob McDonald.

The problem for researchers is that while fecal transplants can be an effective tool, they don't really know enough about how they work. They'd like to understand which microbes are particularly important, and in what proportions. This would allow them to move away from the crude therapy of dosing patients with the complex, mysterious mixture of microbes in a healthy person's poop, and towards a rationally designed mixture of well understood probiotics.

Super poopers

The discovery of super donors, whose feces seems to be particularly efficacious in clinical trials, could help with this problem.

"What people have noticed is that in some studies where they used donations from different individuals, different donors seem to have different effects on recipients," O'Sullivan explained.

In a newly published literature review, O'Sullivan and his colleagues looked at past fecal transplantation trials to find clues to understand what's special about these super donors.

He found that they have greater numbers and varieties of microbes in their stools compared to less effective donors. But they've also found that super donors seem to have certain species of bacteria in their feces that seem to help regulate the entire population of bacteria in the gut.

"If these keystone species can successfully engraft themselves in the patient's gut, it can kickstart processes to change the host's microbiome and lead to a clinical resolution," O'Sullivan explained.

But despite the appeal of this one-stool-fits-all solution, O'Sullivan says there are also other factors at play when it comes to a successful transplant. If the donor is critical, so is the patient.

The interplay of a patient's diet, genetics, combined with their past history all impact how a patient responds to the transplant. Scientists, at this point, still don't know enough how these different factors affect each other.  

Later this year, O'Sullivan will be conducting a new clinical trial to better understand super donors for the treatment of obesity.

From poop to pill

The ultimate goal is to find out what's in "super poop" and duplicate it, so we're not dosing people with feces, but with a carefully cultivated and selected bacterial cocktail.

Emma Allen-Vercoe, a professor in the department of molecular and cellular biology at the University of Guelph, has been working on this problem for the past decade with the help of her "robo-gut," a special device she invented.

The mechanical system mimics the human colon and allows Allen-Vercoe to grow and maintain feces in an artificial environment. It's super handy as she tries to understand the complex microbial interactions in feces, and tries to cultivate difficult-to-grow bacteria.

She has been using it to work on the development of a pill to treat infections with C. difficile, which is now in clinical trials.

"We started off from the idea that we really needed to do something better than feces," Allen-Vercoe said. "So a pill is really just a collection of purified and stabilized microbes that we put into a pill that you can take as an oral capsule."

There are 40 species of bacteria in her pill that are cultivated from healthy super donors. It has greater diversity of strains compared to commercial probiotics, which typically contain only one or a couple of different microbes.

If you pack enough different microbes in a pill, it's much more likely that some will be effective in re-creating a healthy gut ecosystem, Allen-Vercoe explained.  

Instead of looking for critical bacteria to treat a condition, her strategy is to look at the functions of each bacteria and how they benefit the overall microbiome, and include those in her pill.

"You can get away with a subset of an ecosystem that can do the same job," she explained, "and so far, we found 40 species of bacteria in the gut that cover the critical functions important in maintaining a healthy microbiome."

Future research

If all goes well, Allen-Vercoe sees microbial therapeutics being useful in treating a large range of diseases in the future, from inflammatory bowel disease to depression and anxiety.

But she says the field needs to tread carefully because there are still many things that we don't understand.

"We don't really understand the mechanism in many of these diseases and how the microbiome is connected exactly," she said. "So until we understand that, we're not going to be able to treat these diseases effectively."