Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Department of Inflammation & Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Int J Mol Sci. 2024 Jan 29;25(3):1665. doi: 10.3390/ijms25031665.
We aimed to test how the postbiotic butyrate impacts select gut bacteria, small intestinal epithelial integrity, and microvascular endothelial activation during acute ethanol exposure in mice and primary human intestinal microvascular endothelial cells (HIMECs). Supplementation during an acute ethanol challenge with or without tributyrin, a butyrate prodrug, was delivered to C57BL/6 mice. A separate group of mice received 3 days of clindamycin prior to the acute ethanol challenge. Upon euthanasia, blood endotoxin, cecal bacteria, jejunal barrier integrity, and small intestinal lamina propria dendritic cells were assessed. HIMECs were tested for activation following exposure to ethanol ± lipopolysaccharide (LPS) and sodium butyrate. Tributyrin supplementation protected a butyrate-generating microbe during ethanol and antibiotic exposure. Tributyrin rescued ethanol-induced disruption in jejunal epithelial barrier, elevated plasma endotoxin, and increased mucosal vascular addressin cell-adhesion molecule-1 (MAdCAM-1) expression in intestinal microvascular endothelium. These protective effects of tributyrin coincided with a tolerogenic dendritic response in the intestinal lamina propria. Lastly, sodium butyrate pre- and co-treatment attenuated the direct effects of ethanol and LPS on MAdCAM-1 induction in the HIMECs from a patient with ulcerative colitis. Tributyrin supplementation protects small intestinal epithelial and microvascular barrier integrity and modulates microvascular endothelial activation and dendritic tolerizing function during a state of gut dysbiosis and acute ethanol challenge.
我们旨在测试后生丁酸如何影响急性乙醇暴露期间小鼠肠道特定细菌、小肠上皮完整性和微血管内皮细胞激活，以及在原代人肠道微血管内皮细胞（HIMEC）中的作用。在急性乙醇挑战期间，通过补充丁酸前体三丁酸甘油酯或不补充三丁酸甘油酯，向 C57BL/6 小鼠给药。另一组小鼠在急性乙醇挑战前接受 3 天克林霉素治疗。安乐死后，评估血液内毒素、盲肠细菌、空肠屏障完整性和小肠固有层树突状细胞。检测 HIMEC 暴露于乙醇±脂多糖（LPS）和丁酸钠后是否被激活。三丁酸甘油酯补充剂可保护产丁酸微生物免受乙醇和抗生素暴露的影响。三丁酸甘油酯可挽救乙醇诱导的空肠上皮屏障破坏、血浆内毒素升高和肠道微血管内皮细胞黏膜血管地址素细胞黏附分子-1（MAdCAM-1）表达增加。三丁酸甘油酯的这些保护作用与肠道固有层中耐受性树突状反应一致。最后，丁酸钠的预处理和共同处理可减轻溃疡性结肠炎患者 HIMEC 中乙醇和 LPS 对 MAdCAM-1 诱导的直接影响。三丁酸甘油酯补充可保护小肠上皮和微血管屏障完整性，并在肠道菌群失调和急性乙醇挑战期间调节微血管内皮细胞激活和树突状耐受功能。
