Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands.
Mol Nutr Food Res. 2024 Jun;68(11):e2300910. doi: 10.1002/mnfr.202300910. Epub 2024 May 25.
Gut epithelial barrier disruption is commonly observed in Western diseases like diabetes and inflammatory bowel disease (IBD). Enhanced epithelial permeability triggers inflammatory responses and gut microbiota dysbiosis. Reduced bacterial diversity in IBD affects gut microbiota metabolism, altering microbial products such as secondary bile acids (BAs), which potentially play a role in gut barrier regulation and immunity. Dietary fibers such as pectin may substitute effects of these BAs. The study examines transepithelial electrical resistance of gut epithelial T84 cells and the gene expression of tight junctions after exposure to (un)sulfated secondary BAs. This is compared to the impact of the dietary fiber pectin with different degrees of methylation (DM) and blockiness (DB), with disruption induced by calcium ionophore A23187 under both normal and hyperglycemic conditions. Unsulfated lithocholic acid (LCA) and deoxycholic acid (DCA) show a stronger rescuing effect, particularly evident under 20 mM glucose levels. DM19 with high DB (HB) and DM43HB pectin exhibit rescuing effects under both glucose conditions. Notably, DM19HB and DM43HB display higher rescue effects under 20 mM glucose compared to 5 mM glucose. The study demonstrates that specific pectins such as DM19HB and DM43HB may serve as alternatives for preventing barrier disruption in the case of disturbed DCA metabolism.
肠上皮屏障破坏在西方疾病中很常见,如糖尿病和炎症性肠病(IBD)。增强的上皮通透性会引发炎症反应和肠道微生物失调。IBD 中细菌多样性的减少会影响肠道微生物代谢,改变微生物产物,如次级胆汁酸(BAs),这些产物可能在肠道屏障调节和免疫中发挥作用。果胶等膳食纤维可能会替代这些 BAs 的作用。本研究检测了暴露于(未)硫酸化次级 BAs 后肠道上皮 T84 细胞的跨上皮电阻和紧密连接基因表达,并将其与具有不同甲基化(DM)和块状度(DB)程度的膳食纤维果胶的影响进行了比较,在正常和高血糖条件下,用钙离子载体 A23187 诱导破坏。未硫酸化的石胆酸(LCA)和脱氧胆酸(DCA)显示出更强的挽救作用,在 20mM 葡萄糖水平下尤为明显。具有高 DB(HB)和 DM43HB 的 DM19 果胶在两种葡萄糖条件下均具有挽救作用。值得注意的是,与 5mM 葡萄糖相比,DM19HB 和 DM43HB 在 20mM 葡萄糖下显示出更高的挽救作用。该研究表明,特定的果胶,如 DM19HB 和 DM43HB,可能可作为预防 DCA 代谢紊乱时屏障破坏的替代物。