By Marie Rosenthal, MS
Fungal colonization appears to have a symbiotic relationship with Clostridioides difficile that can influence the severity of disease, according to microbiologist Jesus A. Romo, PhD, who discussed his work at ASM Microbe 2024, held in Atlanta.
The role of bacteria in the gastrointestinal tract has been better studied, but fungi colonization also has consequences, according to Dr. Romo, who is an assistant professor in the Department of Molecular Microbiology and Immunology at The University of Texas at San Antonio. Among the many behaviors, fungi can migrate from the GI tract and cause disseminated infections in other areas of the body; and they can reduce the stability of bacterial communities, he explained.
However, fungi, particularly Nakaseomyces glabrata (formerly Candida glabrata), appear to affect C. difficile, Dr. Romo said, although the exact roles and relationship of these two organisms are still being elucidated.
As antibiotic treatment reduces the microorganisms in the gut, allowing C. difficile to proliferate, other organisms can also increase, including N. glabrata.
“After there's a reduction in the healthy microbiota, C. difficile can expand to high numbers, secrete toxins and damage the gastrointestinal epithelium,” Dr. Romo said. “The other thing that antibiotics do is they lead to fungal blooms in the gastrointestinal tract because fungi are not sensitive to antibiotics.”
This change leads to a gut with C. difficile and fungi dominating the environment, which may set the stage for a severe C. difficile infection (CDI).
However, what exactly happens on that stage is open to interpretation because the data are conflicting, he noted. Some studies found that fungi have a role in CDI. Others found it protective—that Candida overgrowth can prevent C. difficile from growing. Still other studies found a negative role, especially if someone is receiving a fecal microbiota transplant. Patients with Candida albicans have higher rates of rejection of the transplant, “presumably due to the presence of the fungus,” he said.
“We don't know what role these fungi are playing in this environment,” Dr. Romo said, but there is evidence of activity.
N. glabrata is not an organism to be trifled with. It’s commonly found in the environment, flowers, soil, water, and animals including migratory birds, and is part of the commensal flora of the human gut. But like C. albicans, it can cause opportunistic infections in immunocompromised people. It can form biofilms and is resistant to commonly used antifungals, particularly the azoles, he explained.
Dr. Romo’s work has been focused on whether N. glabrata plays a role in CDI, and if so, what that role is. He has conducted many studies using several different models to tease out this relationship. In one study, the researchers found they could detect N. glabrata in the same regions as C. difficile throughout the GI tract.
“It appears that this organism can colonize the majority of the gastrointestinal tract. Now, that's important because it aligns with what's been reported for C. difficile previously,” he said, which suggests that N. glabrata would be affected by antibiotic treatment in the same way as C. difficile.
In another study in a mouse model, Dr. Romo and his colleagues gave mice C. glabrata (the study preceded the nomenclature change). Another group of mice received C. difficile and a third group received both pathogens. They were also given antibiotics that increased the risk for C. difficile. Although all the subjects with CDI died, those with CDI and C. glabrata died sooner than the mice with only C. difficile (mSphere 2023;8[4]:e0012223).
“With Candida glabrata alone, the animals don't get sick; they don't lose weight; they just gain weight. The animals with C. diff begin to die at about day 4. But when you have both organisms present, these animals begin to die about two days into the administration of C. difficile, suggesting there's some form of exacerbation of this disease when they're both present,” he said.
Further studies point to an earlier production of toxin in coinfected animals, he explained. Dr. Romo is currently studying the mechanisms underlying this relationship, and although there is still much work to be done, he is sure that both organisms exacerbate CDI.
“We think that C. diff can interact with and exploit N. glabrata directly, and it can benefit by the environment of the GI [tract] that's being modified by [N.] glabrata.”
