Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease
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 o...
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Nature Portfolio
2020
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oai:doaj.org-article:3110da24af8843d099fb67bca2e44e212021-12-02T12:33:04ZAnalysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease10.1038/s41598-020-78340-z2045-2322https://doaj.org/article/3110da24af8843d099fb67bca2e44e212020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78340-zhttps://doaj.org/toc/2045-2322Abstract 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.Anne DarielLucie GrynbergMarie AugerChloé LefèvreTony DurandPhilippe AubertCatherine Le Berre-ScoulAurélien VenaraEtienne SuplyMarc-David LeclairPhiline de VriesGuillaume LevardBenoit ParmentierGuillaume PodevinFrançoise SchmittVéronique CouvratSabine IrtanErik HervieuxThierry VillemagneHubert LardyCarmen CapitoCécile MullerSabine SarnackiJean-François MosnierLouise GalmichePascal DerkinderenHélène BoudinCharlène BrochardMichel NeunlistNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Anne Dariel |
| title |
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| title_short |
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| title_full |
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| title_fullStr |
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| title_full_unstemmed |
Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s disease |
| title_sort |
analysis of enteric nervous system and intestinal epithelial barrier to predict complications in hirschsprung’s disease |
| publisher |
Nature Portfolio |
| publishDate |
2020 |
| url |
https://doaj.org/article/3110da24af8843d099fb67bca2e44e21 |
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