Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China
State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China.
J Endocrinol. 2018 Sep;238(3):231-244. doi: 10.1530/JOE-18-0137. Epub 2018 Jun 25.
Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both and experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both and Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.
内毒素血症与 2 型糖尿病（T2DM）密切相关，是许多糖尿病并发症的罪魁祸首。最近的研究表明，短链脂肪酸（SCFA）丁酸可能在 T2DM 中发挥作用，丁酸是肠道微生物代谢产物。肠道通透性增加是糖尿病性内毒素血症的关键事件。为了研究丁酸是否可以改善糖尿病性内毒素血症，本研究进行了 和 实验。通过 db/db 小鼠实验，确定了丁酸补充对血液 HbA1c 和炎症细胞因子的影响；通过 和 实验，研究了丁酸对肠道屏障完整性和紧密连接蛋白表达的影响。丁酸给药可显著降低 db/db 小鼠的血液 HbA1c、炎症细胞因子和 LPS；HE 染色、免疫组化和 Western blot 检测结果显示，丁酸给药可减少炎症细胞浸润，增加肠道完整性和细胞间黏附分子。通过肠道微生物组分析发现，丁酸可降低肠道微生物组中的厚壁菌门：拟杆菌门比值。在 Caco-2 细胞中，丁酸可显著促进细胞增殖，减少炎症细胞因子的分泌，增强细胞抗氧化应激能力，并维持由 LPS 破坏的上皮单细胞完整性。本研究结果表明，丁酸补充可通过恢复肠道微生物组组成和维持肠道上皮屏障完整性来改善 db/db 小鼠的糖尿病性内毒素血症。
