A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development.
Abstract
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. Under general anesthesia, the rectosigmoid serosa of 5-day-old suckling piglets was exposed to 0.5% benzalkonium chloride solution (BAC, n = 7) or saline (SHAM, n = 5) for 1 h. After surgery, animals returned to their home-cage with the sow and littermates and were studied 21 days later. BAC treatment induced partial aganglionosis with absence of myenteric plexus and reduced surface area of submucosal plexus ganglia (-58%, P < 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%, P < 0.05). Tight junction protein remodeling was observed with decreased ZO-1 (-95%, P < 0.05) and increased claudin-3 and e-cadherin expressions (+197% and 61%, P < 0.05 and P = 0.06, respectively). BAC piglets harbored greater abundance of proinflammatory bacteria (Bil...Continue Reading
References
Intestinal aganglionosis is associated with early and sustained disruption of the colonic microbiome
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