Scientific Reports (Dec 2020)

Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease

  • Anne Dariel,
  • Lucie Grynberg,
  • Marie Auger,
  • Chloé Lefèvre,
  • Tony Durand,
  • Philippe Aubert,
  • Catherine Le Berre-Scoul,
  • Aurélien Venara,
  • Etienne Suply,
  • Marc-David Leclair,
  • Philine de Vries,
  • Guillaume Levard,
  • Benoit Parmentier,
  • Guillaume Podevin,
  • Françoise Schmitt,
  • Véronique Couvrat,
  • Sabine Irtan,
  • Erik Hervieux,
  • Thierry Villemagne,
  • Hubert Lardy,
  • Carmen Capito,
  • Cécile Muller,
  • Sabine Sarnacki,
  • Jean-François Mosnier,
  • Louise Galmiche,
  • Pascal Derkinderen,
  • Hélène Boudin,
  • Charlène Brochard,
  • Michel Neunlist

DOI
https://doi.org/10.1038/s41598-020-78340-z
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 14

Abstract

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Abstract In Hirschsprung’s disease (HSCR), postoperative course remains unpredictable. Our aim was to define predictive factors of the main postoperative complications: obstructive symptoms (OS) and Hirschsprung-associated enterocolitis (HAEC). In this prospective multicentre cohort study, samples of resected bowel were collected at time of surgery in 18 neonates with short-segment HSCR in tertiary care hospitals. OS and HAEC were noted during postoperative follow-up. We assessed the enteric nervous system and the intestinal epithelial barrier (IEB) in ganglionic segments by combining immunohistochemical, proteomic and transcriptomic approaches, with functional ex vivo analysis of motility and para/transcellular permeability. Ten HSCR patients presented postoperative complications (median follow-up 23.5 months): 6 OS, 4 HAEC (2 with OS), 2 diarrhoea (without OS/HAEC). Immunohistochemical analysis showed a significant 41% and 60% decrease in median number of nNOS-IR myenteric neurons per ganglion in HSCR with OS as compared to HSCR with HAEC/diarrhoea (without OS) and HSCR without complications (p = 0.0095; p = 0.002, respectively). Paracellular and transcellular permeability was significantly increased in HSCR with HAEC as compared to HSCR with OS/diarrhoea without HAEC (p = 0.016; p = 0.009) and HSCR without complications (p = 0.029; p = 0.017). This pilot study supports the hypothesis that modulating neuronal phenotype and enhancing IEB permeability may treat or prevent postoperative complications in HSCR.