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

Abstract : 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, 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. Results - 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 (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. Level of evidence -
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https://hal.inrae.fr/hal-02911607
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Submitted on : Tuesday, August 25, 2020 - 4:16:33 PM
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Alexis Pierre Arnaud, Juliette Hascoet, Pauline Berneau, Francis Legouevec, Julien Georges, et al.. A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development. Journal of Pediatric Surgery, American Academy of Pediatrics, 2021, 56 (2), pp.337-345. ⟨10.1016/j.jpedsurg.2020.06.018⟩. ⟨hal-02911607⟩

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