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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-78340-z |
| _version_ | 1818430005634400256 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T15:26:32Z |
| format | Article |
| id | doaj.art-3110da24af8843d099fb67bca2e44e21 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:26:32Z |
| publishDate | 2020-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3110da24af8843d099fb67bca2e44e212022-12-21T22:56:00ZengNature PortfolioScientific Reports2045-23222020-12-0110111410.1038/s41598-020-78340-zAnalysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung’s diseaseAnne Dariel0Lucie Grynberg1Marie Auger2Chloé Lefèvre3Tony Durand4Philippe Aubert5Catherine Le Berre-Scoul6Aurélien Venara7Etienne Suply8Marc-David Leclair9Philine de Vries10Guillaume Levard11Benoit Parmentier12Guillaume Podevin13Françoise Schmitt14Véronique Couvrat15Sabine Irtan16Erik Hervieux17Thierry Villemagne18Hubert Lardy19Carmen Capito20Cécile Muller21Sabine Sarnacki22Jean-François Mosnier23Louise Galmiche24Pascal Derkinderen25Hélène Boudin26Charlène Brochard27Michel Neunlist28University of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADPaediatric Surgery Department, University Hospital of NantesPaediatric Surgery Department, University Hospital of BrestPaediatric Surgery Department, University Hospital of PoitiersPaediatric Surgery Department, University Hospital of PoitiersPaediatric Surgery Department, University Hospital of AngersPaediatric Surgery Department, University Hospital of AngersPaediatric Surgery Department, Hospital of Le MansPaediatric Surgery Department, Armand Trousseau HospitalPaediatric Surgery Department, Armand Trousseau HospitalPaediatric Surgery Department, University Hospital of ToursPaediatric Surgery Department, University Hospital of ToursPaediatric Surgery Department, Necker Enfants Malades HospitalPaediatric Surgery Department, Necker Enfants Malades HospitalPaediatric Surgery Department, Necker Enfants Malades HospitalPathology Department, University Hospital of NantesUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADUniversity of Nantes, INSERM, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMADAbstract 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.https://doi.org/10.1038/s41598-020-78340-z |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-020-78340-z |
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