Translational evaluation of Gelsectan® effects on gut barrier dysfunction and visceral pain in animal models and irritable bowel syndrome with diarrhoea.

IF 5.8 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
United European Gastroenterology Journal Pub Date : 2024-10-01 Epub Date: 2024-08-06 DOI:10.1002/ueg2.12625
Orsolya Inczefi, Hélène Eutamene, Fanny Placide, Valérie Tondereau, Petra Pallagi, Mária Bagyánszki, Nikolett Bódi, Nikolett Gémes, Gábor Szebeni, Tamás Molnár, Vassilia Theodorou, Richárd Róka
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引用次数: 0

Abstract

Background: Gelsectan® is a formulation of xyloglucan (XG), pea protein, grape seed extract (PPGS) and xylo-oligosaccharides (XOS). Our aim was to examine the effect of Gelsectan® on rectal sensitivity in an animal model, abdominal pain in irritable bowel syndrome with diarrhoea (IBS-D) subjects and intestinal permeability in both conditions.

Methods: Animals: Wistar rats received gavage with XOS, XG + PPGS or XG + PPGS + XOS, as a single dose or for 7 days before a partial restraint stress (PRS). Visceromotor response to rectal distension and total gut paracellular permeability to 51Cr-EDTA were assessed. Humans: IBS-D and control patients were involved. After initial colonoscopy with biopsy sampling Gelsectan® was administered to IBS-D patients for 12 weeks. Stool count and pain scores were documented. After treatment, colonoscopy was repeated. The permeability of biopsy samples was measured in Ussing-chambers. Adherent mucus layer, Muc-2 expression as well as TNFα, Interferon IFNγ were evaluated by histology/immunohistochemistry and ELISA assays, respectively.

Results: Animal studies: In control rats, PRS significantly increased visceromotor response as well as gut paracellular permeability. Single dose administration of XG + PPGS + XOS failed to reverse PRS, but 7 days of oral treatment reversed PRS-induced rectal hypersensitivity and gut hyperpermeability. Human studies: Gelsectan® treatment significantly reduced and abdominal pain. Intestinal permeability in IBS-D patients was elevated compared with controls, Gelsectan® restored permeability in the ascendent colon. Periodic acid-Schiff-stained mucus layer was significantly thinner in IBS-D patients compared with controls, In both segments, mucus thickness and the proportion of Muc-2 positive cells were not affected by Gelsectan® treatment. IFNγ tissue level in the sigmoid colon shows modest mucosal inflammation in IBS-D.

Conclusions: Gelsectan® prevented rectal hypersensitivity in rats, abdominal pain in human and intestinal hyperpermeability in rat and human studies respectively. These effects involve restoration of gut permeability. Based on this translational study, Gelsectan® can be considered as an effective therapy for IBS-D symptoms.

Gelsectan® 对动物模型肠道屏障功能障碍和内脏疼痛以及肠易激综合征伴腹泻的影响的转化评估。
背景:Gelsectan® 是一种由木糖(XG)、豌豆蛋白、葡萄籽提取物(PPGS)和木寡糖(XOS)组成的配方。我们的目的是研究 Gelsectan® 对动物模型直肠敏感性、腹泻型肠易激综合征(IBS-D)患者腹痛以及这两种情况下肠渗透性的影响:动物:Wistar大鼠在部分约束应激(PRS)前单次或连续7天灌胃XOS、XG + PPGS或XG + PPGS + XOS。对直肠扩张的粘液运动反应和肠道旁对 51Cr-EDTA 的总通透性进行了评估。人类:参与研究的有肠易激综合征-D 患者和对照组患者。在首次结肠镜检查和活检取样后,给肠易激综合征-D 患者服用 Gelsectan®,为期 12 周。记录大便次数和疼痛评分。治疗结束后,再次进行结肠镜检查。活检样本的渗透性在乌星腔中进行测量。附着粘液层、Muc-2 表达以及 TNFα、干扰素 IFNγ 分别通过组织学/免疫组织化学和酶联免疫吸附试验进行评估:动物实验:在对照组大鼠中,PRS 明显增加了粘液运动反应和肠道旁通透性。单剂量给药 XG + PPGS + XOS 无法逆转 PRS,但 7 天的口服治疗可逆转 PRS 引起的直肠超敏反应和肠道高渗透性。人体研究:Gelsectan® 治疗明显减轻了腹痛。与对照组相比,肠易激综合征-D 患者的肠道渗透性升高,Gelsectan® 可恢复升结肠的渗透性。与对照组相比,肠易激综合征-D 患者的周期性酸-施氏染色粘液层明显变薄;在两个区段,粘液厚度和 Muc-2 阳性细胞的比例不受 Gelsectan® 治疗的影响。乙状结肠中的 IFNγ 组织水平显示,肠易激综合征-D 患者的粘膜炎症并不严重:结论:Gelsectan® 可分别预防大鼠直肠超敏反应、人类腹痛以及大鼠和人类肠道高渗透性。这些效果涉及肠道渗透性的恢复。根据这项转化研究,Gelsectan® 可被视为治疗肠易激综合征-D 症状的有效疗法。
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来源期刊
United European Gastroenterology Journal
United European Gastroenterology Journal GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
10.50
自引率
13.30%
发文量
147
期刊介绍: United European Gastroenterology Journal (UEG Journal) is the official Journal of the United European Gastroenterology (UEG), a professional non-profit organisation combining all the leading European societies concerned with digestive disease. UEG’s member societies represent over 22,000 specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and the exchange of knowledge.
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