Antibodies play a major role in managing gut mycobiota, says study

According to recent research by Weill Cornell Medicine researchers, antibody protection against harmful forms of fungi in the gut might be disrupted in some patients with Crohn’s disease—a condition occurring due to chronic inflammation in the bowel.

Antibodies play a major role in managing gut mycobiota, says study
Illustration of antibodies. Image Credit: Shutterstock.

Earlier research works revealed that the immune system performs a major role in retaining a healthy balance of gut bacteria. In the current study, senior author Dr Iliyan Iliev, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology, and his group from Weill Cornell Medicine analyzed if the immune system might play a role in managing gut fungi.

Fungi, unlike bacteria, can alter their shape in response to environmental conditions, and some forms are harmful to humans. Particularly, a kind of fungus named Candida albicans transforms from a yeast form (non-pathogenic) to a form that generates long, branched structures known as hyphae, capable of invading tissues and causing damage.

The research was published on November 22nd, 2021, in the Nature Microbiology journal.

The researchers discovered that antibodies secreted in the gut help regulate the pathogenesis of C. albicans in healthy individuals. This protective mechanism might be disabled in individuals with Crohn’s disease, resulting in harmful overgrowth of the pathogenic form of the fungus. An intestinal overabundance of C. albicans is linked with inflammatory bowel disease and numerous other conditions that indirectly or directly impact 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. This process is interrupted in patients with Crohn’s disease.”

Dr Iliyan Iliev, Scientist, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine

The researchers, in their analysis, identified that an antibody named secretory immunoglobulin A (slgA) in feces of healthy mice selectively binds to the form of C. albicans with hyphae, preventing its spread. They identified that these antibodies also attach to hyphae in feces from healthy humans.

Those antibodies are preferentially binding to hyphae.”

Itai Doron, Doctoral Candidate, The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine

They particularly bind to sites on the hyphae that generate molecules utilized by these fungi to harm host tissues. However, the antibodies do not attach preferentially to the non-harmful form of the yeast. This indicates that antibodies might aid the body in retaining a healthy balance of gut fungi by inhibiting harmful forms of the fungi from overtaking.

The researchers also identified that patients with Crohn’s disease having severe inflammation in the small intestine and colon have greater levels of anti-fungal antibodies in their blood when compared to healthy adults. However, those antibodies do not appear to be produced at greater levels into the gut to neutralize C. albicans hyphae. Samples obtained from the colons of these patients disclose an overabundance of the fungi with hyphae.

An impairment in this mechanism of control in mice and in patients with Crohn’s disease might be a contributing factor to the increased hyphal growth in the gut.”

Dr Iliyan Iliev, Scientist, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine

Upon addition of anti-fungal antibodies to human cells cultured along with C. albicans the fungi produced fewer hyphae.

Doron states, “It seems that these antifungal antibodies ‘disarm’ hyphae to a degree.”

The findings indicate that analyzing the anti-fungal antibodies therapeutically may be a means to help patients develop an overgrowth of C. albicans. Dr. Iliev remarked that not all patients having this inflammatory bowel disease harbor this kind of fungal overgrowth, however, it might also be a significant contributor to disease in a subset of patients.

Dr. Iliev remarked, “The community of fungi in the gut, specifically C. albicans, is shaping our immunity. We develop these antibodies, and it seems they have a protective role in a specific context.”

Source:
Journal reference:

Doron, I., et al. (2021) Mycobiota-induced IgA antibodies regulate fungal commensalism in the gut and are dysregulated in Crohn’s disease. Nature Microbiology. doi.org/10.1038/s41564-021-00983-z.

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