Gut Fungus Engyodontium Disrupts Protective Bacteria and Worsens Inflammation in Crohn's Disease
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Scientists have identified a common gut fungus called Engyodontium that appears to worsen Crohn's disease by crowding out beneficial bacteria that normally calm the immune system. The fungus disrupts a key protective pathway in which the bacterium Lactobacillus johnsonii produces an amino acid that helps maintain immune-regulating T cells. Patients with Crohn's disease were found to have elevated Engyodontium and reduced levels of Lactobacillus, pointing to a new potential therapeutic target in the gut microbiome.
Abstract
Isolating commensal fungi from mouse intestines has historically been challenging, limiting understanding of their role in intestinal immune homeostasis and inflammatory disease. Using an Fc fusion protein of the C-type lectin receptor Dectin-2, researchers purified the commensal Ascomycota fungus Engyodontium sp. from mouse feces. Engyodontium enhances the antimicrobial activity of colonic neutrophils via the CARD9 pathway and exacerbates colitis by impairing colonization of the beneficial intestinal bacterium Lactobacillus johnsonii.
L. johnsonii produces high levels of l-glutamic acid through expression of the glutaminase-encoding gene glsA, which facilitates regulatory T cell (Treg) expansion via enhanced IL-2 receptor signaling. In human patient samples, individuals with Crohn disease and ulcerative colitis harbored increased Engyodontium and decreased L. johnsonii abundance. Engyodontium directly induced calprotectin expression in human colonic neutrophils, and Crohn disease patients also showed lower levels of l-glutamic acid, which independently supports Treg expansion.
These findings define an Engyodontium-calprotectin axis that opposes the protective Lactobacillus-glutamate-Treg cascade, thereby aggravating colitis. The study identifies commensal Engyodontium-triggered signaling as a potential therapeutic target for mucosal inflammatory diseases including Crohn's disease.