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A common fungus sets the stage for successful fecal microbiota transplantation in people with ulcerative colitis

A recent study found that high levels of a common fungus in the gut could signal whether a microbe-based treatment would be successful for people with ulcerative colitis. Changes or disruptions in the gut’s microbiome—the community of bacteria, viruses, and fungi that naturally inhabit the intestines—have been implicated in inflammatory bowel diseases like ulcerative colitis. One treatment that researchers are investigating is fecal microbiota transplantation (FMT), whereby a sample containing gut microbes from a healthy donor is introduced into a person with colitis to help reestablish a more functional gut microbiome. While FMT has proven to be a successful therapy for people with Clostridioides difficile (C. diff) bacterial infections, with over 90 percent of people cured after a single treatment, FMT is less successful for people with ulcerative colitis: in a recent clinical trial, less than half the participants with colitis experienced remission after FMT. Knowing why the treatment works only in some people is important, because it would allow health care providers to predict which individuals with ulcerative colitis would benefit from FMT as opposed to another treatment strategy. One possibility is that FMT’s success may be dependent upon the makeup of the recipient’s microbiome. For example, FMT is less likely to succeed as a C. diff treatment for people who have high levels of Candida, a type of fungus found in the guts of nearly everyone. Candida is an opportunistic pathogen that can exacerbate inflammation when the immune system is weakened or the microbiome is disrupted. Moreover, high levels of Candida could determine FMT outcomes by affecting the levels of other microbial members of the gut. Thus, like in people with C. diff, high levels of Candida may also play an important role in determining the outcomes of FMT in people with ulcerative colitis.

To determine whether gut microbes such as Candida may be affecting FMT for people with ulcerative colitis, researchers studied the microbiomes of 24 men and women who had received FMT as a trial treatment for the disease. Unlike in people with C. diff infections, the study participants who had higher levels of Candida before FMT were more likely to have improved colitis symptoms and clinical features following treatment. After FMT, levels of Candida—and the immune response against Candida—were lower in these people compared to those who received a placebo. This raises the possibility that introducing gut microbes from healthy donors suppresses the overgrowth of Candida—and the inflammation caused by it—in people with ulcerative colitis. The researchers also found that study participants who had higher pre-FMT levels of Candida were more likely to have higher pre-FMT levels of certain gut bacteria that have been linked to successful FMT outcomes for ulcerative colitis. This suggests that a high level of Candida may create a permissive environment for FMT in people with ulcerative colitis by encouraging the growth of specific gut bacteria in the microbiome. Overall, the results of this study hint of an intricate relationship between Candida and other members of the microbiome, whereby high levels of Candida in people with ulcerative colitis make the microbiome more receptive to FMT. In turn, FMT results in reduced levels of Candida and the inflammation associated with it. In this manner, Candida levels could be a promising marker to predict whether FMT may be effective for people with ulcerative colitis.

Leonardi I, Paramsothy S, Doron I,…Iliev ID. Fungal trans-kingdom dynamics linked to responsiveness to fecal microbiota transplantation (FMT) therapy in ulcerative colitis. Cell Host Microbe 27: 823-829. e3, 2020.

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