Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
J Agric Food Chem. 2024 Nov 6;72(44):24400-24416. doi: 10.1021/acs.jafc.4c04456. Epub 2024 Oct 23.
Dietary fiber is known to promote the production of short-chain fatty acids (SCFAs) by gut bacteria, which can enhance intestinal epithelial barrier function and ameliorate intestinal inflammation in patients with inflammatory bowel disease (IBD). Interestingly, some IBD patients show reduced expression of solute carrier family member 3 (Slc26a3) in intestinal epithelial cells. The objective of this research was to investigate the interaction between SCFAs and Slc26a3 during colitis and assess how this interaction affects intestinal epithelial barrier function. We showed that butyrate alleviated colonic inflammation in a dose-dependent manner in a dextran sulfate sodium salt (DSS)-induced colitis model. Consistent with this, butyrate increased Slc26a3 and tight junction protein levels. In addition, butyrate inhibited histone deacetylase (HDAC) levels and significantly increased the expression of Slc26a3 by the acetylation of histones in Caco-2BBe cells. The utilization of a pan-HDAC inhibitor or inhibitors specific to certain classes of HDACs revealed that butyrate primarily suppressed HDAC8 to blunt the NF-κB pathways and enhance the expression of Slc26a3. Notably, we demonstrated that HDAC8 activation counteracted the beneficial effect of butyrate in DSS-induced colitis. Therefore, we concluded that butyrate improves the expression of Slc26a3 via inhibition of the HDAC8/NF-κB pathway, leading to increased intestinal epithelial barrier function.
膳食纤维已知可促进肠道细菌产生短链脂肪酸 (SCFAs)，从而增强肠上皮屏障功能并改善炎症性肠病 (IBD) 患者的肠道炎症。有趣的是，一些 IBD 患者的肠上皮细胞中溶质载体家族成员 3 (Slc26a3) 的表达减少。本研究旨在探讨 SCFAs 和 Slc26a3 在结肠炎中的相互作用，并评估这种相互作用如何影响肠上皮屏障功能。我们表明，丁酸盐以剂量依赖的方式在葡聚糖硫酸钠盐 (DSS) 诱导的结肠炎模型中减轻结肠炎症。与此一致的是，丁酸盐增加了 Slc26a3 和紧密连接蛋白的水平。此外，丁酸盐通过组蛋白乙酰化抑制组蛋白去乙酰化酶 (HDAC) 水平，并显著增加 Caco-2BBe 细胞中 Slc26a3 的表达。使用 pan-HDAC 抑制剂或特定于某些 HDAC 类别的抑制剂表明，丁酸盐主要抑制 HDAC8 以抑制 NF-κB 途径并增强 Slc26a3 的表达。值得注意的是，我们证明了 HDAC8 的激活抵消了丁酸盐在 DSS 诱导的结肠炎中的有益作用。因此，我们得出结论，丁酸盐通过抑制 HDAC8/NF-κB 途径改善 Slc26a3 的表达，从而增加肠上皮屏障功能。
