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.
Xiaochen Chen, Naschla Gasaly, Marthe T C Walvoort, Paul de Vos
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引用次数: 0
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.
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.