Antimicrobial peptides modulate lung injury by altering the intestinal microbiota
Ahmed Abdelgawad, Teodora Nicola, Isaac Martin, Brian Halloran, Kosuke Tanaka, Comfort Adegboye, Pankaj Jain, Changchun Ren, Charitharth Vivek Lal, Namasivayam Ambalavanan, Amy E. O’Connell, Tamás Jilling, Kent A. Willis
Abstract
BACKGROUND: Mammalian mucosal barriers secrete antimicrobial peptides (AMPs) as critical, host-derived regulators of the microbiota. However, mechanisms that support microbiota homeostasis in response to inflammatory stimuli, such as supraphysiologic oxygen, remain unclear. RESULTS: We show that supraphysiologic oxygen exposure to neonatal mice, or direct exposure of intestinal organoids to supraphysiologic oxygen, suppresses the intestinal expression of AMPs and alters intestinal microbiota composition. Oral supplementation of the prototypical AMP lysozyme to hyperoxia-exposed neonatal mice reduced hyperoxia-induced alterations in their microbiota and was associated with decreased lung injury. CONCLUSIONS: Our results identify a gut-lung axis driven by intestinal AMP expression and mediated by the intestinal microbiota that is linked to lung injury in newborns. Together, these data support that intestinal AMPs modulate lung injury and repair. Video Abstract.