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由LR 32、BL 04和BB 536组成的益生菌混合物通过作用于紧密连接蛋白1来对抗肠易激综合征黏膜介质诱导的通透性增加。

A Probiotic Mixture of LR 32, BL 04, and BB 536 Counteracts the Increase in Permeability Induced by the Mucosal Mediators of Irritable Bowel Syndrome by Acting on Zonula Occludens 1.

作者信息

Barbaro Maria Raffaella, Bianco Francesca, Cremon Cesare, Marasco Giovanni, Stanghellini Vincenzo, Barbara Giovanni

机构信息

IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy.

Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy.

出版信息

Int J Mol Sci. 2025 Mar 15;26(6):2656. doi: 10.3390/ijms26062656.

Abstract

Irritable Bowel Syndrome (IBS) is a disorder of gut- brain interaction characterized by recurrent abdominal pain associated with altered bowel habits. The therapeutic options for IBS patients include the use of probiotics. The aim of this study was to assess the effect of a multi-strain probiotic made up by LR 32, BL 04, and BB 536 (Serobioma, Bromatech s.r.l., Milano, Italy) on an in vitro model of the intestinal epithelial barrier in the presence of mucosal mediators that are released by IBS patients. IBS (n = 28; IBS with predominant diarrhea, IBS-D = 10; IBS with predominant constipation, IBS-C = 9; and IBS with mixed bowel habits, IBS-M = 9) patients, diagnosed according to the Rome IV criteria, and asymptomatic controls (ACs, n = 7) were enrolled. Mucosal mediators that were spontaneously released by colonic biopsies were collected (supernatants). Two doses of Serobioma were tested with/without IBS/AC mediators. RNA was extracted from Caco-2 cells to evaluate the tight junction (TJ) expression. Serobioma (10 CFU/mL) significantly reinforced the Caco-2 monolayer compared to growth medium alone ( < 0.05). IBS supernatants significantly increased Caco-2 paracellular permeability compared to the AC supernatants. The co-incubation of Caco-2 cells with IBS supernatants and Serobioma (10 CFU/mL) avoided the paracellular permeability alterations that were induced by IBS supernatants alone ( < 0.001), and, in particular, IBS-D and IBS-M ones. The co-incubation of Serobioma (10 CFU/mL) and IBS-D supernatants significantly increased ZO-1 expression compared to Caco-2 cells incubated with supernatants alone ( < 0.05), as confirmed via qPCR analyses. Serobioma (10 CFU/mL) counteracts the paracellular permeability changes that are induced by IBS supernatants, in particular IBS-D and IBS-M supernatants, likely modulating ZO-1 expression.

摘要

肠易激综合征(IBS)是一种肠-脑相互作用紊乱的疾病,其特征为反复出现的腹痛并伴有排便习惯改变。IBS患者的治疗选择包括使用益生菌。本研究的目的是评估由LR 32、BL 04和BB 536(意大利米兰的Serobioma公司,Bromatech s.r.l.)组成的多菌株益生菌在存在IBS患者释放的黏膜介质的情况下对肠上皮屏障体外模型的影响。根据罗马IV标准诊断的IBS患者(n = 28;以腹泻为主的IBS,IBS-D = 10;以便秘为主的IBS,IBS-C = 9;以及排便习惯混合的IBS,IBS-M = 9)和无症状对照者(ACs,n = 7)被纳入研究。收集结肠活检组织自发释放的黏膜介质(上清液)。测试了两剂Serobioma在有/无IBS/AC介质情况下的效果。从Caco-2细胞中提取RNA以评估紧密连接(TJ)的表达。与单独的生长培养基相比,Serobioma(10 CFU/mL)显著增强了Caco-2单层(<0.05)。与AC上清液相比,IBS上清液显著增加了Caco-2细胞旁通透性。Caco-2细胞与IBS上清液和Serobioma(10 CFU/mL)共同孵育可避免单独IBS上清液(<0.001),特别是IBS-D和IBS-M上清液诱导的细胞旁通透性改变。与单独用上清液孵育的Caco-2细胞相比,Serobioma(10 CFU/mL)与IBS-D上清液共同孵育显著增加了ZO-1的表达(<0.05),这通过qPCR分析得到证实。Serobioma(10 CFU/mL)可抵消IBS上清液,特别是IBS-D和IBS-M上清液诱导的细胞旁通透性变化,可能是通过调节ZO-1的表达来实现的。

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