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
Cristina Pardo-Camacho,
John-Peter Ganda Mall,
Cristina Martínez,
Marc Pigrau,
Elba Expósito,
Mercé Albert-Bayo,
Elisa Melón-Ardanaz,
Adoración Nieto,
Bruno Rodiño-Janeiro,
Marina Fortea,
Danila Guagnozzi,
Amanda Rodriguez-Urrutia,
Inés de Torres,
Ignacio Santos-Briones,
Fernando Azpiroz,
Beatriz Lobo,
Carmen Alonso-Cotoner,
Javier Santos,
Ana M. González-Castro,
Maria Vicario
Affiliations
Cristina Pardo-Camacho
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
John-Peter Ganda Mall
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Cristina Martínez
Vascular and Renal Translational Research Group, Lleida Institute for Biomedical Research Dr. Pifarré. Foundation (IRBLleida), Av. Alcalde Rovira Roure 80, 25198 Lleida, Spain
Marc Pigrau
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Elba Expósito
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Mercé Albert-Bayo
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Elisa Melón-Ardanaz
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Adoración Nieto
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Bruno Rodiño-Janeiro
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Marina Fortea
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Danila Guagnozzi
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Amanda Rodriguez-Urrutia
Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
Inés de Torres
Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
Ignacio Santos-Briones
Facultat Ciències de la Salut, Universitat Ramon LLull-Blanquerna, C/Padilla 326, 08025 Barcelona, Spain
Fernando Azpiroz
Department of Gastroenterology, Vall d’Hebron Hospital Universitari, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Beatriz Lobo
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Carmen Alonso-Cotoner
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Javier Santos
Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Ana M. González-Castro
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
Maria Vicario
Laboratory of Translational Mucosal Immunology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca, Passeig Vall d’Hebron 119-129, 08035 Barcelona, Spain
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.