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Abstract
Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1–47.2]) were compared with those of 16 HVs (age: 39.0 [31.0–46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = − 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFβ1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.
Clinical Trials: NCT02440984 and NCT03054415.
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1 CHRU Pontchaillou, Université de Rennes 1, Service d’Explorations Fonctionnelles Digestives, Rennes Cedex, France; TENS, Université de Nantes, The Enteric Nervous System in Gut and Brain Disorders INSERM, Nantes, France (GRID:grid.488848.0); Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), CHU Rennes, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984); CHRU Pontchaillou, Centre Référence Maladies Rares Spina Bifida, Rennes, France (GRID:grid.414271.5)
2 Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), CHU Rennes, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984); CHRU Pontchaillou, Université de Rennes 1, Service des Maladies de l’Appareil Digestif, Rennes, France (GRID:grid.411154.4); Institut Numecan, INSERM, INRAE, Univ Rennes, Rennes, France (GRID:grid.410368.8) (ISNI:0000 0001 2191 9284)
3 TENS, Université de Nantes, The Enteric Nervous System in Gut and Brain Disorders INSERM, Nantes, France (GRID:grid.488848.0)
4 CHRU Pontchaillou, Service d’Anatomopathologie, Rennes, France (GRID:grid.414271.5)
5 Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), CHU Rennes, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984); CHRU Pontchaillou, Centre Référence Maladies Rares Spina Bifida, Rennes, France (GRID:grid.414271.5); CHRU Pontchaillou, Service d’Urologie, Rennes, France (GRID:grid.414271.5)
6 CHRU Pontchaillou, Université de Rennes 1, Service des Maladies de l’Appareil Digestif, Rennes, France (GRID:grid.414271.5)
7 Institut Numecan, INSERM, INRAE, Univ Rennes, Rennes, France (GRID:grid.410368.8) (ISNI:0000 0001 2191 9284)
8 Université de Nantes, CHU Nantes, INSERM, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Nantes, France (GRID:grid.277151.7) (ISNI:0000 0004 0472 0371); CRNH-Ouest Mass Spectrometry Core Facility, Nantes, France (GRID:grid.277151.7)
9 Plateforme H2P2, Université de Rennes, Rennes, France (GRID:grid.410368.8) (ISNI:0000 0001 2191 9284)
10 Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), CHU Rennes, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984)
11 CHRU Pontchaillou, Université de Rennes 1, Service d’Explorations Fonctionnelles Digestives, Rennes Cedex, France (GRID:grid.411154.4)
12 Service de Chirurgie Pédiatrique, CHU Marseille, Marseille, France (GRID:grid.414336.7) (ISNI:0000 0001 0407 1584)
13 Inserm, CIC 1414 (Centre d’Investigation Clinique de Rennes), CHU Rennes, Rennes, France (GRID:grid.411154.4) (ISNI:0000 0001 2175 0984); CHRU Pontchaillou, Centre Référence Maladies Rares Spina Bifida, Rennes, France (GRID:grid.414271.5); CHRU Pontchaillou, Université de Rennes 1, Service des Maladies de l’Appareil Digestif, Rennes, France (GRID:grid.414271.5)