Qiao Zhenyi, Wang Xiaohua, Zhang Huanchang, Han Jin, Feng Huafeng, Wu Zhengjun
State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China.
State Key Laboratory of Dairy Biotechnology, Shanghai Engineering Research Center of Dairy Biotechnology, Postdoctoral Workstation of Bright Dairy-Shanghai Jiao Tong University, Dairy Research Institute, Bright Dairy & Food Co., Ltd., Shanghai, China.
Front Microbiol. 2020 Dec 22;11:568805. doi: 10.3389/fmicb.2020.568805. eCollection 2020.
Chronic low-grade inflammation is widely involved in the development and progression of metabolic syndrome, which can lead to type 2 diabetes mellitus (T2DM). Dysregulation of proinflammatory and anti-inflammatory cytokines not only impairs insulin secretion by pancreatic β-cells but also results in systemic complications in late diabetes. In our previous work, metabolites produced by sp. nov. BD3526, which were isolated from Tibetan yak milk, demonstrated antidiabetic effects in Goto-Kakizaki (GK) rats. In this work, we used single-cell RNA sequencing (scRNA-seq) to further explore the impact of BD3526 metabolites on the intestinal cell composition of GK rats. Oral administration of the metabolites significantly reduced the number of adipocytes in the colon tissue of GK rats. In addition, cluster analysis of immune cells confirmed that the metabolites reduced the expression of interleukin (IL)-1β in macrophages in the colon and increased the numbers of dendritic cells (DCs) and regulatory T (T) cells. Further mechanistic studies of DCs confirmed that activation of the WNT/β-catenin pathway in DCs promoted the expression of IL-10 and transforming growth factor (TGF)-β, thereby increasing the number of T cells.
慢性低度炎症广泛参与代谢综合征的发生和发展，而代谢综合征可导致2型糖尿病（T2DM）。促炎细胞因子和抗炎细胞因子的失调不仅会损害胰腺β细胞的胰岛素分泌，还会导致糖尿病晚期的全身并发症。在我们之前的研究中，从西藏牦牛奶中分离出的新种BD3526产生的代谢产物在Goto-Kakizaki（GK）大鼠中显示出抗糖尿病作用。在这项研究中，我们使用单细胞RNA测序（scRNA-seq）进一步探究BD3526代谢产物对GK大鼠肠道细胞组成的影响。口服这些代谢产物可显著减少GK大鼠结肠组织中脂肪细胞的数量。此外，免疫细胞的聚类分析证实，这些代谢产物降低了结肠巨噬细胞中白细胞介素（IL）-1β的表达，并增加了树突状细胞（DC）和调节性T（T）细胞的数量。对DC的进一步机制研究证实，DC中WNT/β-连环蛋白通路的激活促进了IL-10和转化生长因子（TGF）-β的表达，从而增加了T细胞的数量。
