Antibodies Help Keep Gut Fungi Under Control

Antibody protection against harmful forms of fungi in the gut may be disrupted in some patients with Crohn’s disease—a condition caused by chronic inflammation in the bowel—according to a new study by Weill Cornell Medicine investigators. The study was published in Nature Microbiology.

The investigators found 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, causing a harmful overgrowth of the pathogenic form of the fungus. An intestinal overabundance of Candida albicans is associated with inflammatory bowel disease and several other conditions that directly or indirectly affect the gastrointestinal tract. “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 Iliyan Iliev.  “This process is interrupted in patients with Crohn’s disease.” In their experiments, the investigators found that secretory immunoglobulin A (slgA) in feces from healthy mice selectively binds to the form of C. albicans with hyphae, stopping its spread. They found these antibodies also bind hyphae in feces from healthy humans.

“Those antibodies are preferentially binding to hyphae,” said collaborator Itai Doron. 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 non-harmful 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.

The results suggest that exploring anti-fungal antibodies therapeutically might be a way to help patients who develop an overgrowth of C. Aabicans. 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 concluded. “We develop these antibodies, and it seems they have a protective role in a specific context.”