Inflammatory bowel disease (IBD), a family of autoimmune diseases of the gut, has set researchers on a hunt to understand which microbes are responsible for launching the immune system into overdrive. Previous studies have demonstrated and pointed to gut fungus as a culprit in the inflammatory bowel disease, Crohn’s disease. Now, Weill Cornell Medicine researchers report that antibody protection against harmful forms of fungi in the gut may be disrupted in some patients with Crohn’s disease.
The findings are published in the journal Nature Microbiology, in a paper titled, “Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn’s disease.”
“Secretory immunoglobulin A (sIgA) plays an important role in gut barrier protection by shaping the resident microbiota community, restricting the growth of bacterial pathogens and enhancing host protective immunity via immunological exclusion,” the researchers wrote. “Here, we found that a portion of the microbiota-driven sIgA response is induced by and directed towards intestinal fungi.”
Iliyan Iliev, PhD, associate professor of immunology in medicine in the division of gastroenterology and hepatology, and his team investigated if the immune system plays a key role in managing gut fungi.
The team discovered that antibodies that are secreted in the gut help control the pathogenesis of Candida albicans in healthy individuals and that this protective mechanism may be disabled in people with Crohn’s disease.
“We found that antibodies secreted in the gut are involved in maintaining specific intestinal fungi such as C. albicans in its benign, so-called commensal form,” said Iliev, who is also a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “This process is interrupted in patients with Crohn’s disease.”
The researchers observed that an antibody called secretory immunoglobulin A (slgA) in feces from healthy mice selectively binds to the form of C. albicans with hyphae, stopping its spread.
“Those antibodies are preferentially binding to hyphae,” said Itai Doron, a doctoral candidate in the laboratory. Specifically, they bind to sites on the hyphae that produce molecules used by these fungi to harm host tissues. The antibodies, however, don’t bind preferentially to the nonharmful form of the yeast. This suggests that antibodies may help the body maintain a healthy balance of gut fungi by preventing harmful forms of the fungi from taking over.
Their findings suggest that exploring anti-fungal antibodies therapeutically might be a way to help patients who develop an overgrowth of C. albicans. Iliev noted that not all patients with this inflammatory bowel disease have this type of fungal overgrowth, but it may be an important contributor to disease in a subset of patients.
“The community of fungi in the gut, specifically C. albicans, is shaping our immunity,” Iliev said. “We develop these antibodies, and it seems they have a protective role in a specific context.”
“Our findings indicate that antifungal sIgA produced in the gut can play a role in regulating intestinal fungal commensalism by coating fungal morphotypes linked to virulence, thereby providing a protective mechanism that might be dysregulated in patients with Crohn’s disease,” concluded the researchers.