According to new research published by scientists from Weil Cornell Medicine, common fungi in the gut teaches our immune system how to respond and fend off their more dangerous relatives. While the breakdown of the process may leave people susceptible to deadly fungal infections.

Good Fungi in the Gut

A new study published in the journal Cell on February 5th suggests a twist in the complex relationship between humans and microbes. The research published by scientists from Weill Cornell Medicine, New York, and Necker Hospital for Sick Children, Paris, may point towards novel therapies that could help combat the rise of drug-resistant pathogens.

The novel discovery stems from work on inflammatory bowel diseases, which often causes patients to carry abnormally larger fungi populations in their guts. These patients would often develop a strong antibody response against mannan, a common molecule for a wide range of fungal species.

However, Dr. Iliyan Iliev, lead author and associate professor in the Division of Gastroenterology at Weill Cornell Medicine, notes that healthy controls in the conducted studies show some level of anti-fungal antibodies. 

Lliev says, "There was no actual evidence for fungal infections in the healthy individuals that we examined, so we started thinking about the possible function of those antibodies."


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Studying Gut Fungi

To understand how healthy patients had levels of anti-fungal antibodies, researchers developed a platform. This allowed them to determine which antibodies target gut fungi in the blood of patients.

The team detected a strong response against yeast Candida albicans. This caused patients to develop antibodies against fungus in the bloodstream despite not developing blood-borne fungal infections. 

Instead, scientists observed that immune cells appeared to transport fungal antigens to the patient's spleen that stimulates the production of circulating antibodies in the patient's bloodstream.

Dr. Lliev says, "Those fungi just educate that immune response."

Patients with suppressed immune systems, such as those with a history of organ transplants and some cancer patients, gut fungi invade the bloodstream that causes life-threatening infections. The team mimicked this process by treating mice with immunosuppressive drugs.

When Candida species colonized the gut of the mice, fungus moved rapidly into the bloodstream causing fatal infections.

Treating the mice with purified anti-fungal antibodies from other animals protected the immunosuppressed mice from infections. The same technique worked when used against either Candida albicans or other emerging pathogenic yeats Candida Auris, which became a major cause of fungal diseases in immunosuppressed patients and the elderly in recent years.

Patients with suppressed immunity show a decline in anti-fungal antibodies that leave them vulnerable to fungal infections. New therapies that involve stimulating the production of anti-fungal antibodies or injection of purified antibodies into the patients' bloodstreams could potentially help combat the increasingly common infection.

"Many fungal infections in immunosuppressed patients and elderly patients are happening by translocation of pathogenic Candida species front the gastrointestinal tracts, and the survival rates upon systemin spreading are alarmingly low," says Dr. Lliev.

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