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Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome : Jejunal Barrier Alterations Underlying Clinical Manifestations
Pardo-Camacho, Cristina (Universitat Autònoma de Barcelona. Facultat de Medicina)
Ganda Mall, John-Peter (Department of Biomedical and Clinical Sciences, Linköping University)
Martínez, Cristina (Institut de Recerca Biomèdica de Lleida)
Pigrau Pastor, Marc (Universitat Autònoma de Barcelona)
Expósito, Elba (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Albert-Bayo, Mercé (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Melón-Ardanaz, Elisa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nieto Ruiz, Adoración (Hospital Universitari Vall d'Hebron)
Rodiño-Janeiro, Bruno (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Fortea, Marina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Guagnozzi, Danila (Hospital Universitari Vall d'Hebron)
Rodríguez-Urrutia, Amanda (Centro de Investigación Biomédica en Red de Salud Mental)
de Torres, Inés (Hospital Universitari Vall d'Hebron)
Santos-Briones, Ignacio (Universitat Ramon Llull. Facultat de Ciències de la Salut Blanquerna)
Azpiroz Vidaur, Fernando (Hospital Universitari Vall d'Hebron)
Lobo Álvarez, Beatriz (Hospital Universitari Vall d'Hebron)
Alonso Cotoner, Carmen (Universitat Autònoma de Barcelona)
Santos, Javier (Hospital Universitari Vall d'Hebron)
González Castro, Ana Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vicario Perez, Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Fecha: 2022
Resumen: Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.
Ayudas: European Commission 848228
Ministerio de Economía y Competitividad CP18/00116
Instituto de Salud Carlos III PI17/01443
Ministerio de Economía y Competitividad PI15/00301
Ministerio de Economía y Competitividad PI17/0190
Instituto de Salud Carlos III PI19/01643
Ministerio de Economía y Competitividad CPII16/00031
Ministerio de Sanidad y Consumo CB06/04/0021
Agencia Estatal de Investigación SAF2016-76648-R
Generalitat de Catalunya 2014SGR1285
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès
Documento: Article ; recerca ; Versió publicada
Materia: Intestinal plasma cells ; Intestinal glycocalyx ; IBS-D ; Mucosal ultrastructure ; Intestinal barrier dysfunction ; Mucosal nerve fibres
Publicado en: Cells, Vol. 11 (june 2022) , ISSN 2073-4409

DOI: 10.3390/cells11132046
PMID: 35805133


19 p, 2.0 MB

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