A new mouse study by scientists at Weill Cornell Medicine has revealed that a specific group of fungi residing in the intestines can protect against intestinal injury and influence social behavior. The findings extend a growing body of work identifying a “gut-immunity-brain axis.”

The study, “Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity,” is published in the journal Cell, and revealed a novel set of molecular signals connecting fungi in the gut to their host’s cells throughout the body, including immune cells and neurons.

“Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies,” wrote the researchers. “Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans.”

“We have made a direct link between a major immune pathway induced by fungi in the lining of the intestine and signals in the nervous system that impact animal behavior,” explained senior author Iliyan Iliev, PhD, associate professor of immunology in medicine in the division of gastroenterology and hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

Examining this system in a mouse model, the scientists mapped the locations of different fungi within the intestine and found that a unique group of fungi tends to accumulate at specific sites near the gut epithelium.

“There was fortification of those barrier functions when we added that specific fungal community to mice,” Iliev noted.

The researchers also observed that mice carrying the fungal community in their gut displayed more social behavior than animals without these fungi.

Both effects appear to stem from the animals’ own T cells. The fungi caused T cells to secrete two immune signaling proteins, cytokines IL-22 and IL-17. Fungi-induced IL-22 acts locally in the epithelium, strengthening its barrier function, while IL-17 enters the bloodstream and eventually reaches neurons, which have receptors for it.

“There is this harmony—a kind of communication between or across different types of organisms,” Iliev said.

The researchers hope to explore that communication network further. “We are trying to go deeper into the mechanisms of this interaction, looking at the signals that are involved at the neuronal level in different brain regions,” said lead author Irina Leonardi, PhD, an instructor of immunology in medicine in Iliev’s laboratory at the Jill Roberts Institute for Research in IBD.

“This opens a whole new area to explore,” Iliev concluded.

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