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Chitin-glucan improves important pathophysiological features of irritable bowel syndrome

World Journal of Gastroenterology 2024年第16期30卷 2258-2271页

作者： Caroline Valibouze Caroline Dubuquoy philippe chavatte Michaël Genin Veronique Maquet Salvatore Modica Pierre Desreumaux Christel Rousseaux Department of Digestive Surgery and Transplantation Lille UniversityLille 59037France Intestinal Biotech Development Facultéde MédicineLille 59045France U1286-INFINITE-Institute for Translational Research in Inflammation Universitéde LilleLille 59000France ULR 2694-METRICS Évaluation des Technologies de santéet des Pratiques MédicalesUniversity of LilleLille 59000France KitoZyme SA Institution SociétéAnonymeZone 2Parc des Hauts SartsRue de MilmortHerstal 4040Belgium Hepato-Gastroenterology Department Lille University HospitalLille 59037France

BACKGROUND Irritable bowel syndrome(IBS)is one of the most frequent and debilitating conditions leading to gastroenterological referrals.However,recommended treatments remain limited,yielding only limited therapeutic gains.Chitin-glucan(CG)is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority.To provide an alternative approach to managing patients with IBS,we performed preclinical molecular,cellular,and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS.AIM To evaluate the roles of CG in visceral analgesia,intestinal inflammation,barrier function,and to develop computational molecular models.METHODS Visceral pain was recorded through colorectal distension(CRD)in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS[15 milligrams(mg)/kilogram(kg)]in 33 Sprague-Dawley rats.Intracolonic pressure was regularly assessed during the 9 wk-experiment(weeks 0,3,5,and 7)in animals receiving CG(n=14)at a human equivalent dose(HED)of 1.5 g/d or 3.0 g/d and compared to negative control(tap water,n=11)and positive control(phloroglucinol at 1.5 g/d HED,n=8)groups.The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate(DSS)administered in their drinking water during 14 d.HT-29 cells under basal conditions and after stimulation with lipopolysaccharide(LPS)were treated with CG to evaluate changes in pathways related to analgesia μ-opioid receptor(MOR),cannabinoid receptor 2(CB2),peroxisome proliferator-activated receptor alpha,inflammation[interleukin(IL)-10,IL-1b,and IL-8]and barrier function[mucin 2-5AC,claudin-2,zonula occludens(ZO)-1,ZO-2]using the real-time PCR method.Molecular modelling of CG,LPS,lipoteichoic acid(LTA),and phospholipomannan(PLM)was developed,and the ability of CG to chelate microbial pathogenic lipids

关键词： Chitin-glucan Irritable bowel syndrome Abdominal pain Inflammation Intestinal barrier Molecular modelling Microbial cell walls chelation

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High Plasma Concentrations of Sclerostin, an Inhibitor of the Wnt Signaling Pathway, in Young Horses Affected by Osteochondrosis

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Open Journal of Orthopedics 2014年第12期4卷 335-342页

作者： Didier Serteyn Luis Mendoza Charlotte Sandersen Isabelle Caudron David Piquemal Pascale chavatte-Palmer Jean-philippe Lejeune Equine Clinic University of Liege Liege Belgium Equine Research and Development Center Mont-le-Soie Belgium Center of Oxygen Research and Development University of Liege Liege Belgium Computational Biology Institut (IBC) Montpellier France Acobiom Montpellier France INRA URM1198 Biologie du Développement et Reproduction F-78350 Jouy en Josas Paris France

Osteochondrosis (OC) is a developmental disease in horses with a significant impact on the horse’s welfare and performance. The early disturbance of enchondral ossification progresses to inflammatory and healing process in older horses. Metabolic pathway analysis showed an obvious dysregulation of several signaling pathways related to cartilage formation and cartilage repair such as Wnt/β-catenin, Indian hedgehog and TGF-β signaling pathways. Other regulated genes appeared to be involved in high carbohydrate diet, abnormal insulin metabolism or inflammation. Sclerostin is an osteocyte-secreted soluble antagonist of the Wnt/β-catenin signaling pathway. It is crucial for osteoblast development and activity and is increased in naturally occurring lesions of equine osteochondrosis. The aim of this study is to compare the circulating sclerostin levels between OC-affected (n = 20) and healthy horses (n = 19). A significant linear regression between plasma sclerostin and age is observed especially in the healthy young horses. The mean plasma sclerostin concentration is significantly higher in young horses suffering from osteochondrosis compared to the control horses. These results reinforce the possible role of the Wnt/β-catenin signaling pathway in the OC pathogeny. The inhibition of this essential pathway could disturb the osteo-chondral differentiation. More studies are currently needed to define the eventual clinic interest of plasma sclerostin as future biomarker in bone and cartilage diseases.

关键词： Sclerostin Osteochondrosis Wnt/β-Catenin Pathway Horse Equine Osteochondrosis

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