Read Caption
Clostridium difficile, by CDC/ Lois S. Wiggs

Infusion of pseudo-poo cures gut infections in two women

People swap bacteria all the time—through sneezes and coughs, through hugs and sex, or through touching the same surfaces. Then there are people who swap bacteria because a doctor deliberately transplants faeces from one into the other.

This isn’t a bizarre medical perversion. It’s usually a life-saving gambit. Faecal transplants—which are exactly what they sound like—are used to treat people who suffer from intense diarrhoea following rounds of antibiotics. The goal is simple: recalibrate the beneficial bacteria in a person’s gut to fight off the ones that are causing them harm.

It’s the loss of these beneficial microbes that’s thought to cause the diarrhoea in the first place. Our guts are teeming with bacteria, which outnumber our own cells and play vital roles of our lives. They help us to digest our food and to keep harmful species from moving in. But we risk destroying these intestinal tenants when we take antibiotics to treat an illness. That allows species like Clostridium difficile, which causes severe diarrhoea, to move in. Without the protection afforded by our gut bugs, we leave ourselves open to gastro-catastrophe.

The idea behind faecal transplants is to fight bacteria with bacteria—to crowd out C.difficile by restoring a well-functioning microbial community in our guts. And what better source than the colon of another healthy person? A few hundred C.difficile patients have been given stool infusions, often because they have run out of options. And it works! More than 90 percent of these people make a full recovery.

But faecal transplants have hardly become common practice. The procedure faces regulatory hurdles since it doesn’t involve a typical drug or device. By its nature, it is very hard to standardise and test through randomised clinical trials—the gold standard of medicine. There are concerns about spreading new diseases along with the helpful bacteria. The stool needs to be freshly collected and used within several hours. And, understandably, there’s the “ick factor” (for that reason, many people prefer that the donor be a spouse or relative).

To circumvent these obstacles, Elaine Petrof from Kingston General Hospital and Gregory Gloor from the University of Western  Ontario have developed a pseudo-poo—a blend of 33 different gut bacteria that mimics the community found in a healthy gut. This “stool substitute” can be cooked up again and again according to the same recipe, and infused into patients without any of the extra faecal matter that makes such transplants so viscerally off-putting or potentially dangerous. Think of it as a rectally applied yoghurt.

“We had a lot of cases of recurrent C.difficile in our hospital,” says Petrof. “These patients were receiving stool transplants, which, although very effective, seemed like a rather crude and primitive method. We thought we could improve on it while still maintaining the same scientific concept.”

Petrof and Gloor based their substitute on the gut bacteria of a healthy 41-year-old woman. They isolated 62 species from her bowels and excluded any that showed even mild signs of antibiotic resistance—those aren’t microbes you want to be deliberately applying to someone’s gut. Thirty-three species remained, which Petrof and Gloor balanced according to their typical proportions in a healthy gut.

The result is a standardised bacterial broth that’s clear of any other disease-causing microbes or viruses, and that can be applied as an enema. (I can go for years without reading the words “drizzled throughout the transverse colon as the colonoscope was withdrawn” in a paper again.)

So far, the team have tested their mixture—which they charmingly call “RePOOPulate”—on two patients, both women in their seventies. One had spent 18 months in hospital with C.difficile. Ten days after receiving her stool substitute, her bowel movements were back to normal and C.difficile had been eradicated. The second woman was fighting her third bout with C.difficile—she too resumed normal bowel movements within 3 days of treatment.  

Colleen Kelly from Brown University, who has used faecal transplants to treat 90 people in the last 5 years, is excited by the study. “Identifying a suitable donor can be difficult in some patients,” she says, as well as time-consuming and expensive. “And some doctors face institutional barriers that prevent them from offering [faecal transplants].  If a safe, effective product was available, many more patients could be treated.

Petrof and Gloor are clear that this is a pilot study. It’s promising that the two patients recovered and suggests that a specially concocted brew of microbes, rather than whole faeces, can be used to treat C.difficile. But with such small numbers, and no comparison with other treatments or with standard faecal transplants, it’s impossible to say if the stool substitutes are a more effective option. After all, faecal transplants have “set a very high bar for any therapy,” says Alexander Khoruts from the University of Minnesota, who has performed many of them on his own patients.

The team are now planning to do longer experiments with animals to understand how the stool substitutes remodel an ailing gut community, as well as testing other bacterial mixtures in patients. “People are different, so the optimal mixture may vary from patient to patient,” says Petrof.

Longer studies are a must. “We do not know possible long-term risks that may be associated with “synthetic” mixtures,” says Khoruts, especially since gut bacteria could affect the risk of obesity, immune disorders, and other conditions. Using actual faeces would pose similar risks but “at least we can screen donors for these conditions. Making up mixtures creates an element of unknown.”

However, Khoruts praises the team’s approach. “It stands far above the quasi-scientific field of probiotics as we know them today,” he says. “Another plus is that there is greater potential for securing intellectual property with this approach, which could enhance chances of commercialization.”

“With only two subjects, the study is fairly preliminary,” says Rob Knight from the University of Colorado, who studies gut bacteria. “But the general concept of designing communities that can counteract C.difficile, rather than relying on transplants of poorly characterized faecal material, is certainly very important. It’s good to see advances in this area.”

Reference: Petrof, Gloor, Vanner, Weese, Carter, Daigneault, Brown, Schroeter & Allen-Vercoe. 2013. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome

More on gut bacteria: