The Fifth Department of Pediatrics Medicine, Cangzhou Central Hospital, Cangzhou, PR China.
The First Department of Pediatrics Medicine, Cangzhou Central Hospital, Cangzhou, PR China.
Kaohsiung J Med Sci. 2018 Mar;34(3):134-141. doi: 10.1016/j.kjms.2017.11.002.
The intestinal mucosal barrier (IMB) enables the intestine to provide adequate containment of luminal microorganisms and molecules while preserving the ability to absorb nutrients. In this study, we explored the effect of brain-derived neurotrophic factor (BDNF) on IMB function and gut microbiota in mice. BDNF gene knock-out mice (the BDNF group) and wild-type mice (the BDNF group) were selected. The gut microbiota of these mice was analyzed by denaturing gradient gel electrophoresis (DGGE) assay. The ultrastructure of the ileum and the colonic epithelium obtained from decapitated mice were observed by transmission electron microscopy. The protein expression of epithelial tight junction proteins, zonula occludens-1 (ZO-1) and occludin was detected by immunohistochemistry staining. The protein expression of claudin-1 and claudin-2 was determined by Western blotting. The DGGE band patterns of gut microbiota in the BDNF group were significantly different from that in the BDNF group, which indicated that the BDNF expression alters the gut microbiota in mice. Compared with the BDNF group, the BDNF group presented no significant difference in the ultrastructure of ileal epithelium; however, a significant difference was observed in the colonic epithelial barrier, manifested by decreased microvilli, widening intercellular space and bacterial invasion. Compared with the BDNF group, the expression of ZO-1 and occludin in the BDNF group was significantly decreased. The expression of claudin-1 in the BDNF group was significantly reduced, while the expression of claudin-2 was elevated. These findings indicate that BDNF preserves IMB function and modulates gut microbiota in mice.
肠道黏膜屏障 (IMB) 使肠道能够充分容纳腔道微生物和分子，同时保持吸收营养物质的能力。本研究旨在探讨脑源性神经营养因子 (BDNF) 对小鼠 IMB 功能和肠道微生物群的影响。我们选择了 BDNF 基因敲除小鼠（BDNF 组）和野生型小鼠（BDNF 组）。通过变性梯度凝胶电泳 (DGGE) 分析这些小鼠的肠道微生物群。通过透射电子显微镜观察断头小鼠回肠和结肠上皮的超微结构。通过免疫组织化学染色检测上皮紧密连接蛋白、闭合蛋白-1 (ZO-1) 和紧密连接蛋白的蛋白表达。通过 Western 印迹法测定 claudin-1 和 claudin-2 的蛋白表达。BDNF 组的肠道微生物群 DGGE 条带模式与 BDNF 组明显不同，这表明 BDNF 表达改变了小鼠的肠道微生物群。与 BDNF 组相比，BDNF 组回肠上皮的超微结构无明显差异；然而，在结肠上皮屏障中观察到明显差异，表现为微绒毛减少、细胞间隙增宽和细菌入侵。与 BDNF 组相比，BDNF 组的 ZO-1 和紧密连接蛋白的表达明显降低。BDNF 组 claudin-1 的表达明显降低，而 claudin-2 的表达升高。这些发现表明 BDNF 可维持 IMB 功能并调节小鼠肠道微生物群。
