A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development

Background Hirschsprung-associated enterocolitis physiopathology likely involves disturbed interactions between gut microbes and the host during early neonatal period. Our objective was to create a porcine model of iatrogenic aganglionosis evaluate impact enteric nervous system (ENS) on microbiota intestinal barrier postnatal development. Methods Under general anesthesia, rectosigmoid serosa 5-day-old suckling piglets exposed 0.5% benzalkonium chloride solution (BAC, n = 7) or saline (SHAM, 5) for 1 h. After surgery, animals returned their home-cage with sow littermates were studied 21 days later. Results BAC treatment induced partial absence myenteric plexus reduced surface area submucosal ganglia (−58%, P < 0.05) in one third circumference. Epithelial permeability this zone increased (conductance +63%, FITC-dextran flux +386%, horseradish-peroxidase +563%, 0.05). Tight junction protein remodeling observed decreased ZO-1 (−95%, claudin-3 e-cadherin expressions (+197% 61%, 0.05 0.06, respectively). harbored greater abundance proinflammatory bacteria (Bilophila, Fusobacterium) compared SHAM lumen. Conclusions This large animal demonstrates that hypoganglionosis is associated dramatic defects function establishment bacteria. Level evidence