756 Skin wounding alters the gut microbiome by inducing antimicrobial peptide and mucin production from intestinal epithelia

Intestinal and skin microflora can influence several systemic health behaviors. In this study, we hypothesized that gut tissue microbiota are linked, control the microbiota. To test this, compared intestinal responses in mice to co-housed littermates with full-thickness incisions on back or K14Cre-targeted expression of HYAL-1 epidermis. The latter represent a skin-specific model hyaluronidase activity produced by wounding but without inflammatory stress response. Both interventions greatly exacerbated disease when were subsequently challenged oral Dextran sulfate sodium salt(DSS ) (60% vs 0% mortality, 11-fold induction IL6 survivors, p<.001). DSS response was dependent microbiome as Germ-free SPF given Vancomycin rescued from effects injury K14HYAL1. 16S rDNA sequencing feces confirmed altered showed relative decrease gram-positive bacteria including protective bifidobacterium. Mechanistically, could be explained results spatial transcriptomics using 10X Visium colon wounded K14HYAL1 had increased Mucin 2(Muc2) Antimicrobial Peptide Regenerating Family Member 3(Reg3). qPCR immunochemistry validated Muc2 Reg3b transverse colon. Furthermore, modeled addition 6.8kDa hyaluronan fragments epithelial cells (HT-29), showing these HA resulted 1.7 fold greater 2 Reg3a (p<.01) vitro. Since mucin Reg3 known regulate intestine, findings demonstrate how alters susceptibility disease.