Endogenous fungi regulate host lipid metabolism to promote intestinal wound repair 2968

Abstract Description Intestinal tissue repair is vital for restoring mucosal homeostasis after injury. While the role of endogenous bacteria in promoting tissue repair is well-recognized, the involvement of nonbacterial microbes such as fungi is poorly understood. Here, we demonstrate that select endogenous fungi promote mucosal healing in distinct murine models of intestinal injury and repair. Using unbiased metabolomics, we identified increased levels of a host-derived lipid metabolite, palmitoylethanolamide (PEA), in response to endogenous intestinal fungi. We show that PEA acts via the PPARα receptor to suppress IL-1 signaling and limit neutrophil recruitment, thereby facilitating mucosal healing in mice. Importantly, the PEA/PPARα axis is perturbed in inflamed intestinal lesions from patients with inflammatory bowel disease (IBD). Our work uncovers a previously unappreciated role of endogenous fungi in modulating host lipid metabolism to promote intestinal repair and reveals novel insights into the pathophysiology of IBD. Topic Categories Mucosal and Regional Immunology (MUC)