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