Fecal Transplants: a New Treatment for IBD

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    Linda Ann Sasser has had ulcerative colitis since she was 20, but it wasn’t until May 2019, about 30 years later, that her condition hit a low point: not only did she have a major flare-up of chronic inflammatory bowel disease (IBD), but on top of it, she had Clostridioides difficile (or C. diff), a highly contagious bacterial infection that causes severe diarrhea and inflammation of the colon. “I became really, really sick with bloody diarrhea 30 times a day and chronic stomach pain,” Sasser says. While hospitalized for 12 days, she was given oral steroid medications, which didn’t help, then IV steroid medications, which gradually improved her ulcerative colitis flare-up. The next challenge was to treat the C. diff infection. The doctors tried antibiotics, which didn’t get the job done; Sasser’s abdominal pain was incessant, and the diarrhea would come on so suddenly that she often couldn’t get to the bathroom in time. “I was at the point where I said, ‘Just take out my colon,’” she recalls. Her doctor told her about another treatment that might help: fecal microbiota transplantation (FMT), which is exactly what it sounds like: fecal matter (as in: stool) from a healthy donor is transplanted into the body of someone like Sasser in the hope that it will improve her health.
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    Sasser didn’t hesitate to opt in, because nothing else had worked for her, so she had FMT through a colonoscopy. The first try didn’t work, so four days later, she had a second FMT procedure, which worked splendidly. “After the procedure, it was a breath of fresh air to not have blood in my stool or stomach pain, and I had normal poops for the first time in my life,” says Sasser, now 51, who owns a dog-grooming business in Sparta, N.C. “The transplant cured the C. diff and made the colitis 100 times better. It has really changed my life.”

    That successful treatment stems from a new understanding and appreciation that’s emerged in recent years about the role gut bacteria play in human health. The gut is home to trillions of microorganisms—including bacteria, viruses, fungi and other microbes—that influence everything from digestion, metabolism and immune function to the development and progression of diseases like obesity, diabetes, inflammatory disorders, cancer, arthritis and depression. The presence of a diverse array of helpful microorganisms in the gut contributes to good health and homeostasis. By contrast, when an imbalance occurs in the microbiota population—whether it’s because of a loss of beneficial micro-organisms, an increase in potentially harmful ones and/or a decline in the overall diversity of microbiota—this leads to what’s called dysbiosis. Think of a lush and thriving garden that is home to a variety of plants, flowers and trees that is overtaken by weeds and fungi—that’s the equivalent of dysbiosis in the gut microbiome. (The microbiome refers to the billions of bacteria that live inside the human digestive tract.) “Any imbalance in the microbiome will cause inflammation and influence pro-inflammatory cascades in the body,” explains Dr. Amy Barto, an associate professor of gastroenterology at the Duke University School of Medicine and director of its Fecal Microbiota Transplantation Program.

    Now doctors and researchers are harnessing the power of the microbiome, treating certain gut infections like C. diff and other recalcitrant medical conditions through fecal microbiota transplantation. “FMT is the ultimate mega-probiotic—an entire microbial ecosystem is transplanted and able to restore or restructure the gut microbiota,” says Dr. Monika Fischer, a gastroenterologist and an associate professor of medicine at Indiana University in Indianapolis.

    Read: It’s Not Yet Clear How to Boost the Microbiome. But Diet Is the Best Bet

    The ick factor

    Once upon a time, it would have been hard to imagine that anyone would be clamoring for the opportunity to have another person’s stool put into their body. It would have been viewed as disgusting, perhaps even gagworthy. These days, there’s a growing demand for healthy feces from human donors to treat C. difficile, in particular, as well as to investigate its potential to treat other medical conditions that can occur both inside and outside the gastrointestinal tract. While the burgeoning use of FMT may seem like a wonder of modern medicine, the practice reportedly dates back to ancient China, where “yellow soup” was used to treat cases of severe food poisoning and diarrhea.

    Doctors say that patients who are likely to benefit from FMT don’t usually turn up their noses at the prospect. For one thing, “these people with recurrent C. difficile infection are so miserable and so isolated because they can’t stop going to the bathroom—they find [FMT] life-saving,” says Dr. Sahil Khanna, a professor of medicine and a consultant in the division of gastroenterology and hepatology at the Mayo Clinic.

    As unpalatable as a fecal microbiota transplant may seem, the process is actually simple and fairly well disguised, because the recipient is asleep and not consciously aware of what’s being infused into their body. After stool is obtained from a donor, it’s screened for infectious diseases. If it passes muster, it’s processed, then often frozen until the day of the transplant. Then the stool is thawed to room temperature, and usually inserted into the recipient’s intestine during a colonoscopy. Alternatively, some providers deliver the stool through a nasogastric tube, an enema or a capsule that can be swallowed, notes Khanna, who runs the Mayo Clinic’s FMT program. These days, many centers rely on stool from OpenBiome, a nonprofit stool bank in Cambridge, Mass., that provides frozen stool that has been rigorously screened and can be shipped to medical facilities for clinical use.

    Right now, FMT is considered an experimental therapy—that is, it has not been approved by the Food and Drug Administration (FDA) for any uses; however, the FDA exercises “enforcement discretion” regarding the use of FMT to treat C. difficile infections that haven’t responded to standard treatments (such as use of the antibiotics fidaxomicin or vancomycin), provided that donors are thoroughly screened and patients are thoroughly informed about the potential benefits and risks of FMT. Meanwhile, it has become a hot area for research for IBD, obesity, cardiovascular disease, auto-immune disorders, diabetes, metabolic syndrome and other medical conditions. “This is a new frontier for how we think about illness and medication by manipulating the gut microbiome,” Khanna says.

    “For C. difficile, FMT is a godsend,” says Dr. Byron Vaughn, an associate professor of medicine and co-director of the Inflammatory Bowel Disease Program at the University of Minnesota in Minneapolis. “I think in 10 years, we’re going to move from it being a third-line therapy to a first-line therapy, and maybe even used preventatively in those who are at high risk for C. difficile,” due to frequent antibiotic use or advancing age, for example.

    For other gastrointestinal conditions, including IBDs such as ulcerative colitis and Crohn’s disease, FMT may be a promising treatment too, but the jury is still out. “The overarching theme is that both of these diseases involve an abnormal immune response to gut bacteria in a host with a genetic susceptibility, and that leads to inflammation in the colon and small intestine,” Vaughn explains. “Inflammation starts to shape your gut bacteria—and [the effects] get circular very quickly.” The idea is that FMT would stop that unfortunate cycle.

    Sometimes it does, according to studies, but it’s not a sure thing. A study in a 2015 issue of the journal Gastroenterology found that a significantly greater percentage of patients with active ulcerative colitis who were treated with FMT experienced remission, compared with those who were given a placebo. By contrast, a study in a 2020 issue of the journal Microbiome examined whether treating patients with Crohn’s disease who experienced a clinical remission after being given an oral corticosteroid with a single FMT treatment would sustain the remission. While the incidence of flares was lower in the FMT group than the placebo group, the goal of achieving a greater than 60% similarity with the donor’s microbiota didn’t happen for any of the patients.

    Moreover, as promising as it seems to be in some instances, it’s important to note that FMT is not without risks. If it’s administered through a colonoscopy, there’s a risk of perforation of the colon, as there is with any colonoscopy. Even with diligent screening of donor stool, there’s the possibility that certain infections and diseases could be transmitted through FMT, says Khanna, who notes that he’s aware of a few cases of E. coli that were transmitted through FMT. Some people end up with irritable bowel syndrome after fecal transplantation. There have also been studies showing that IBD worsens following FMT in approximately 15% of patients.

    Read more: Here’s Everything You Need to Know About Gut Health

    Unanswered questions remain

    One of the ultimate questions is: How effective is FMT for conditions other than C. difficile? “We have the data for C. diff—it clearly works,” says Dr. Colleen Kelly, an associate professor of medicine at the Warren Alpert Medical School of Brown University and one of the principal investors for the FMT National Registry. “For other conditions, we need more clinical trials.” For one thing, C. difficile is an acute infection, whereas inflammatory bowel disorders such as ulcerative colitis and Crohn’s disease are chronic conditions. “C. difficile is a homogeneous disease with a direct connection to gut dysbiosis—we know that fixing the imbalanced microbiota will cure the infection,” Fischer says. “Other gastrointestinal disorders are more complex. We have no idea if the dysbiotic flora are a consequence of the disease, or if they play a role in the development of disease.” In other words, whether changes in the gut microbiome are a cause or consequence of IBD, for example, isn’t known.

    There’s also a fair amount of variability in people’s responses. A study in a 2019 issue of JAMA investigated the use of FMT via colonoscopy followed by two enemas over seven days among adults with mild to moderate ulcerative colitis, and found that 32% achieved steroid-free remission by the eight-week follow-up. That’s impressive, but hardly a cure-all. Meanwhile, studies for other medical conditions haven’t been as successful. In a study in a 2020 issue of PLOS Medicine, researchers investigated whether taking weekly oral FMT capsules containing the stool of healthy, lean donors for six weeks would alter gut microbiota and improve metabolic outcomes in obese adults. While the FMT capsules led to shifts in gut microbiota, the subjects didn’t experience significant changes in their body weight, body composition or insulin sensitivity, compared with those who took a placebo, after 12 weeks. Another lingering concern: whether FMT increases the risk for other diseases over the long haul isn’t known. “We know a lot about the short-term safety issues, but not the long term,” Barto says. If FMT produces a permanent change in someone’s microbiome, what would that portend for the person’s future health risks? The answer isn’t clear. “There’s a theoretical concern that if the microbiome is transferred, it might transfer a predilection to certain diseases, such as obesity, diabetes, or metabolic syndrome,” says Dr. Eamonn Quigley, chief of gastroenterology and hepatology at Houston Methodist Hospital. “The list could be endless, because nearly every disease has been linked to the microbiome.”

    Even with these unknowns, researchers and private companies are looking ahead to the various possibilities. At least one company, Seres Therapeutics, has already developed and is testing oral medications that contain spores of bacteria that naturally occur in the human gut, as a way of treating C. difficile infection, ulcerative colitis and other ailments. “The landscape of FMT is evolving,” Barto says. “The possibility of treating more chronic diseases is really exciting.”

    Still, experts say, it would be a mistake to let enthusiasm for the treatment’s possibilities get ahead of the science. “I really believe in this therapy and believe we’re at the edge of a new horizon in medicine—but it needs to be taken slowly and carefully,” Kelly says. If the proper amount of caution isn’t exercised, there’s a risk that FMT could transmit diseases or infections that aren’t currently being screened for. There’s also a concern that excitement about FMT could cause people to overlook other standard treatments that have been shown to be effective for various conditions.