Protective Effects of Human Milk Oligosaccharides (hMOs) on Analgesic, Nonsteroidal Anti-inflammatory Drugs (NSAIDs)-Induced Disruption of Gut Barrier Integrity in Cocultures Mimicking Neuro-Gut Epithelial Cell Crosstalk.

IF 4.5 2区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY
Xiaochen Chen, Naschla Gasaly, Marthe T C Walvoort, Paul de Vos
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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin alter gut microbiota composition and disrupt intestinal integrity, increasing the risks of inflammatory bowel disease (IBD). Gut barrier function is regulated by a complex crosstalk between different cell types, including epithelial cells and cells from the enteric nervous system (ENS). Human milk oligosaccharides (hMOs), particularly 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), can regulate intestinal barrier function, but their roles in neuroepithelial crosstalk under NSAID stress remain unclear. This study focused on hMOs' direct epithelial effects to explore their potential in microbiota-independent effects caused by the NSAID indomethacin. T84 colorectal carcinoma cells were cocultured with SH-SY5Y neuroblastoma cells in ratios of 29:1 and 14:1. We evaluated the protective role of hMOs in indomethacin-induced barrier disruption. We found that indomethacin reduced transepithelial electrical resistance (TEER), disrupted F-actin organization, and decreased tight junction (TJ) protein expression. Pretreatment with 2'-FL and 3-FL protected against these effects, particularly in cocultures with a higher nerve cell ratio of 14:1, restoring TEER, F-actin integrity, and claudin-1 expression. These findings highlight the therapeutic potential of 2'-FL and 3-FL in directly maintaining barrier integrity in intestinal neuroepithelial cocultures during NSAID treatment.

人乳寡糖(hMOs)对镇痛、非甾体抗炎药(NSAIDs)诱导的模拟神经-肠道上皮细胞串扰共培养中肠道屏障完整性破坏的保护作用
像吲哚美辛这样的非甾体抗炎药(NSAIDs)会改变肠道微生物群的组成,破坏肠道完整性,增加炎症性肠病(IBD)的风险。肠道屏障功能受不同细胞类型(包括上皮细胞和肠神经系统细胞)之间复杂的串扰调节。人乳寡糖(hMOs),特别是2'-焦糖乳糖(2'- fl)和3-焦糖乳糖(3- fl),可以调节肠道屏障功能,但它们在非甾体抗炎药应激下的神经上皮互扰中的作用尚不清楚。本研究的重点是hMOs的直接上皮效应,以探索其在非甾体抗炎药吲哚美辛引起的微生物非依赖性效应中的潜力。将T84结直肠癌细胞与SH-SY5Y神经母细胞瘤细胞按29:1和14:1的比例共培养。我们评估了hMOs在吲哚美辛诱导的屏障破坏中的保护作用。我们发现,吲哚美辛降低了经上皮电阻(TEER),破坏了f -肌动蛋白组织,降低了紧密连接(TJ)蛋白的表达。用2'-FL和3-FL预处理可以防止这些影响,特别是在高神经细胞比例为14:1的共培养中,可以恢复TEER、F-actin完整性和claudin-1表达。这些发现强调了2'-FL和3-FL在非甾体抗炎药治疗期间直接维持肠道神经上皮共培养屏障完整性方面的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Molecular Nutrition & Food Research
Molecular Nutrition & Food Research 工程技术-食品科技
CiteScore
8.70
自引率
1.90%
发文量
250
审稿时长
1.7 months
期刊介绍: Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.
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