1. Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS-A possible association with microbiota?
- Author
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Christer Peterson, Susanna Walter, Maite Casado-Bedmar, Carl Mårten Lindqvist, Marie Carlson, Olga Biskou, Åsa V. Keita, Felipe Meira de-Faria, Olga Bednarska, and Purnika Damindi Ranasinghe
- Subjects
0301 basic medicine ,HIGHLIGHTED ARTICLE ,fecal eosinophil‐derived neurotoxin ,Immunology ,Eosinophil-Derived Neurotoxin ,Gastroenterology and Hepatology ,Biology ,Microbiology in the medical area ,Irritable Bowel Syndrome ,03 medical and health sciences ,0302 clinical medicine ,Eosinophil activation ,medicine ,Extracellular ,bacteria ,eosinophil cationic protein ,irritable bowel syndrome ,fecal eosinophil-derived neurotoxin ,Mikrobiologi inom det medicinska området ,Gastroenterologi ,Immunology and Allergy ,Humans ,Eosinophil degranulation ,Irritable bowel syndrome ,Eosinophil cationic protein ,Mucous Membrane ,Bacteria ,Microbiota ,Degranulation ,Cell Biology ,Eosinophil ,medicine.disease ,Pathophysiology ,Eosinophils ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis - Abstract
Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota. Funding Agencies|Apotekare Hedberg Foundation; Magnus Bergvall Foundation [2018-02604]; Bengt Ihre Foundation [SLS-788111, SLS-882561]; Ruth and Richard Julin Foundation [2017-00350, 2019-00347]; County Council of Ostergotland [Lio-934618]; Mucosa Infection and Inflammation Center-MIIC; Medical Faculty, Uppsala University, Uppsala Sweden
- Published
- 2022