Antimicrobial peptides modulate lung injury by altering the intestinal microbiota

Abstract

Mammalian mucosal barriers secrete antimicrobial peptides (AMPs) as critical host-derived regulators of the microbiota. However, mechanisms that support homeostasis of the microbiota in response to inflammatory stimuli such as supraphysiologic oxygen remain unclear. Here, we show that neonatal mice breathing supraphysiologic oxygen or direct exposure of intestinal organoids to supraphysiologic oxygen suppress the intestinal expression of AMPs and alters the composition of the intestinal microbiota. 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. Our results identify a gut-lung axis driven by intestinal AMP expression and mediated by the intestinal microbiota that is linked to lung injury. Together, these data support that intestinal AMPs modulate lung injury and repair.

Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota

“…Antimicrobial peptides play a critical role in regulating the stability of the host gut microbiota. The damage to ileal epithelial cells resulting from hyperoxia exposure is associated with the downregulation of antimicrobial peptide expression [100]. On the contrary, hypoxia caused by COPD results in gastrointestinal integrity damage, and low active glucose transport and reduced protein digestion and absorption cause the disturbance in the intestinal flora along with the decrease in the synthesis of SCFAs and the concentration of acetic acid in serum, which reversely aggravates the severity of the disease [101].…”