Published On August 31, 2017
WHEN SOMEONE HAS TO UNDERGO A PROTRACTED COURSE OF ANTIBIOTICS—during an organ transplant, for instance—the natural balance of microorganisms in the gut can suffer. That sometimes clears the way for the intestinal tract to be colonized by less savory travelers. Clostridium difficile (C. diff) is one such bacterium, and unchecked it can cause severe diarrhea, pain, high fever and death.
For stubborn cases of infection with C. diff, in the last seven or so years, researchers have increasingly turned to an unconventional treatment: a slurry of feces from a healthy donor, inserted into the colon. This infusion of microbes, so the thinking went, might recolonize the gut and crowd out the C. diff bacterium. Over the past several years, fecal microbiota transplants have achieved remarkable success in several high-profile studies and have challenged standard thinking about how to treat C. diff infection (“From the Bottom Up,” Fall 2014).
Now researchers are asking whether there are other problems a fecal transplant might help solve. Could a dose of healthy bacteria, for instance, protect against dangerous drug-resistant microbes? The bleakest forecasts predict that these stubborn bacteria—microbes such as carbapenem-resistant Enterobacteriaceae (CRE) and methicillin-resistant Staphylococcus aureus (MRSA), which often breed in hospitals and prey on patients with compromised systems—will claim more lives by the year 2050 than cancer does. So research teams around the world are exploring whether fecal transplants can be a successful alternative to new antibiotics.
“The prospect of treating antibiotic-resistant infections with fecal transplant is exciting,” says Colleen Kraft, an infectious disease specialist at Emory University Hospital in Atlanta and co-leader of a clinical trial to test the procedure in kidney transplant patients colonized by drug-resistant bacteria. “It’s like moving someone back to before they got all these antibiotics and reached a drug-resistant state and starting them all over with a normal, healthy gut.”
A healthier gut may prove to be a formidable barrier to infection. Even when drug-resistant microbes are present in a healthy person, microbial diversity can keep those pathogens in check. “A subset of our controls had quite a few antibiotic-resistant microbes in their systems,” says Karen Madsen, director of the Centre of Excellence for Gastrointestinal Inflammation and Immunity Research at the University of Alberta in Canada. But because those subjects’ microbiomes were vibrant and diverse, she says, “they weren’t causing the hosts problems.”
Madsen’s study, published in Clinical Infectious Diseases in March 2016, used fecal transplant treatments in C. diff patients as a starting point for examining its effects on other harmful microbes. Researchers looked at the microbiomes of 20 patients with recurrent C. diff and found that, before the treatment, those patients had a larger quantity and greater diversity of antibiotic-resistant bacteria than did 87 healthy controls and three stool donors whose feces were transplanted into the C. diff patients. After one to two fecal transplants via colonoscopy, all 20 patients saw not only the elimination of their C. diff, but also a reduction in symptoms associated with drug-resistant bacteria. The microbiomes remained healthy and diverse for up to a year following the transplant.
“Fecal transplant seems like a good tool that could be used, not only for eradication of C. difficile but also for removing other drug-resistant bacteria,” Madsen says.
Researchers at the Medical University of Warsaw in Poland conducted a similar study that looked at patients undergoing treatment for bone marrow malignancies. Because those patients required high doses of antibiotics, their guts were especially prone to colonization by antibiotic-resistant bacteria and subsequent infection. The team treated 20 cancer patients with fecal transplant, delivered via a tube that threaded through the nose and into the gut. Within the first month of the procedure, drug-resistant bacteria were completely eliminated in 75% of the patients, and many of the rest had the bugs partly eliminated, according to results published in Clinical Infectious Diseases in March 2017. The group has achieved similar or better results in patients with heart and kidney disease, says Jarosław Biliński, a hematologist at the Medical University of Warsaw and co-author of the study. “I’m sure the strategy can be extended to anyone colonized with antibiotic-resistant bacteria,” Biliński says.
A randomized, placebo-controlled pilot study to test some of these ideas is under way at Atlanta’s Emory University Hospital, led by Kraft and Tanvi Dhere, a gastroenterologist at Emory Clinic. Their study extends the treatment to another vulnerable group: kidney transplant recipients, who are prone to urinary tract infections that can lead to rejection of the new kidneys and sepsis. The researchers will give a fecal enema to patients who have recovered from infection with CRE and/or vancomycin-resistant Enterococcus (VRE), but who still harbor the bacteria in their gut. After the fecal transplant, the researchers will test for rates of colonization with CRE and VRE.
Although all donor samples are heavily screened for the presence of pathogens before being used, fecal transplant does carry some theoretical risks, including the possibility that a harmful virus or bacteria could be passed along from a donor. In addition, notes Madsen, a transplant could have other unintended effects—such as a propensity to obesity, for example. (Some bacterial populations indeed do have an association with higher body weights.) “There is much that we don’t yet know,” she says. “We are all proceeding with caution.”
But the promise of helping vulnerable patients deal with life-threatening infections means that, for now, fecal transplants may prove worth the risk—and a good topic for further, more widespread investigation.
Stay on the frontiers of medicine
- From the Bottom Up
Infusing colons with donated feces has led to remarkable cures and big questions about what’s safe and what’s next.
- Allies Within
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- A Killer Still on the Loose
MRSA infections are down by more than half, and new treatments are on the way. But the pathogen still takes a deadly toll.