Fecal Transplants to Cure Infections—A Modern Take on a 1,700-Year-Old Idea
Bacteriotherapy sounds a lot more amenable of a term than "fecal transplant," yet they're both treatments that use bacteria itself to cure or treat infections. Fecal transplants, specifically, are an up-and-coming treatment option for a potentially deadly and difficult-to-treat diarrheal infection called Clostridium difficile.
Fecal transplants were first developed during the 4th century when a Chinese medicine doctor gave a mixture of human feces by mouth to patients who had severe diarrhea from food poisoning. It was effective and hailed as a miracle. Not surprisingly (can you imagine?), the practice fell out of favor.
Fast forward to modern medicine. Antibiotics have changed many diseases from deadly to curable. However, those same antibiotics can kill off the colonies of good gut bacteria while killing off a dangerous infection. One way to get good bacteria to grow again is to "recolonize" them with bacteriotherapy, which is similar to, but a little less gag-inducing, than the 1,700-year-old practice of eating feces.
The human intestinal system contains about 300-500 species of bacteria—and lots of them. Your gut contains about 10 trillion bacteria per gram of stool.
Gut bacteria play important roles in digestion, immunity, and protection against other infectious organisms. When these gut bacteria are killed off, it is important to repopulate the gut to keep those important functions running smoothly. This repopulation may be one of the most effective ways to treat tough intestinal infections.
Clostridium difficile infections usually occur after treatment with antibiotics, but can also crop up in people who have a chronic illness or in the elderly. These two groups usually have fewer good bacteria in their gut, which leaves them open to infection by more dangerous bacteria such as C. difficile.
C. difficile infection (CDI) is a bacterial infection that causes the large intestine (colon) to become inflamed. People with CDI can have watery diarrhea, fever, abdominal pain, nausea, and loss of appetite. A C. difficile infection is very hard to treat effectively. The first episodes of CDI are treated with the antibiotics like metronidazole or vancomycin.
It is estimated that the CDI returns in up to 35% of treated people. In up to 65% of those treated patients, the disease keeps coming back. The inability to cure CDI in many patients has led the search for alternative treatment. Fecal transplants are not a common treatment for CDI, but they are becoming increasingly popular.
"Fecal transplantation is not commonly performed for C. difficile infection, but interest in this procedure is increasing rapidly," Lawrence J. Brandt, Professor of Medicine and Surgery at Albert Einstein College of Medicine in New York, said in a 2012 interview in the journal Gastroenterology & Hepatology. "I now receive approximately 5–8 telephone calls or e-mails per week from patients or doctors who want to know about fecal transplantation."
Originally, fecal transplants were done using feces from a donor the patient chose. Transplants from a relative were more effective than a fecal transplant from an unrelated healthy volunteer. Donors were carefully screened for diseases, antibiotic use, travel outside the country, and other activities that might cause make them unhealthy or make the bacteria in their feces unsuitable.
Feces were mixed with water, salt solution, yogurt, milk, or a salt solution mixed with fiber. The prepared feces were given during a process where a scope was inserted into the colon, called a colonoscopy, or by a tube that was inserted into the gastrointestinal system through the patient's nose. These processes are still used, but since both sound uncomfortable, disgusting, and can be risky, improvements have been made.
People who volunteer to donate feces can now be screened to see what types and amounts of bacteria are in their feces. And feces can now be put into swallowable capsules or freeze dried making it easier and less risky to administer. Advances are being made to screen the donor feces to contain or omit certain bacteria. In that way, the treatment may be customized for each patient.
The first patient was entered into a clinical trial on January 17, 2017, being conducted at the Mayo Clinic in Rochester, Minnesota, to test the effectiveness of an oral capsule formulated to treat C. difficile infections.
In a news release from the Mayo Clinic, Sahil Khanna, MBBS, gastroenterologist at Mayo Clinic and principal investigator on the study, said the advantages of an oral capsule were its stability at room temperature and the flexibility for at-home treatment.
Fecal transplants used for CDI have cures rates of about 92 percent. About 89% are cured after just one treatment. The reason this process works so well isn't completely understood. It is believed that the transplanted microorganisms restore the types of bacteria and bacterial function missing in the intestines.
A study published in the New England Journal of Medicine showed that fecal transplantation worked better than the antibiotic vancomycin to prevent multiple recurrences in people who had a C. difficile infection in their colon.
A scientific review of fecal transplants done by Gough, Saikh, and Manges in 2011 found that these types of transplants could also be used to treat patients with inflammatory bowel disease. The studies showed improvement of symptoms in 100% of the patients who received the transplant with no relapses or deaths. The authors also noted that mixtures of bacteria grown in the laboratory have also been successful in treating recurrent CDI and other intestinal disorders.
The Food and Drug Administration has not approved fecal transplants as standard treatment for any infection or disease. They do, however, allow doctors to perform the procedure if they tell the patient the procedure is investigational, get the patient's informed consent, and discuss the risks.
It's possible that fecal transplants could treat additional diseases. Researchers are developing more methods to screen donor fecal matter and match it to the needs of the patient. Bacteria grown in the laboratory may be developed for treating CDI, instead of using donor feces.
A recent clinical trial released in the American Society for Microbiology's mBio journal, led by Michael Sadowsky, director of the BioTechnology Institute at the University of Minnesota, compared transplant of fecal material from healthy patients with transplant of the patient's own stool microbes. The study involved 27 patients with recurring C. difficile infection. About 90% of the patients who received transplants from healthy volunteers were cured. The surprising result was that several patients who received their own stool were also cured.
The research team found that patients who showed improvement after transplantation with their own feces had a higher amounts of bacteria from the Clostridium XiVa clade and Holdemania bacteria in their samples. This finding may help clinicians understand how to personalize treatment so each patient has the best chance at a cure.
But, at the end of the road, popularity of fecal transplants may all come down to patient acceptance. It might be a lot easier for a doctor to get a patient to swallow a capsule of freeze dried fecal matter than getting them to accept an enema of someone else's feces.