Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development
Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development
复制标题
DOI：
10.1016/j.chom.2018.11.002
复制
发表时间：
2018-12-12
影响因子：
30.3
通讯作者：
Kweon, Mi-Na
中科院分区：
文献类型：
--
作者：
Lee, Yong-Soo;Kim, Tae-Young;Kweon, Mi-Na
共生体在肠道内稳态中发挥着不可或缺的作用，但其潜在的机制仍然难以捉摸。为了阐明产乳酸菌（LAB）在肠干细胞（ISC）介导的上皮发育中的作用，我们用LAB型共生菌如双歧杆菌和乳杆菌喂养小鼠。在这里，我们表明，LAB型共生体的管理显着增加了扩展的ISCs，潘氏细胞和杯状细胞。乳酸通过潘氏细胞和肠基质细胞的Wnt/β-连环蛋白信号刺激ISC增殖。此外，缺乏乳酸脱氢酶活性的植物乳杆菌菌株，其在乳酸产生中是缺陷的，引起较少的ISC增殖。用LAB型共生体或乳酸盐预处理保护小鼠对由放射和化疗药物联合治疗引起的肠道损伤作出反应。在缺乏乳酸G蛋白偶联受体Gpr 81的小鼠中发现ISC介导的上皮发育受损。我们的研究结果表明，LAB型共生体衍生的乳酸在促进ISC介导的上皮细胞发育中起着关键作用，在Gpr 81依赖的方式。
Symbionts play an indispensable role in gut homeostasis, but underlying mechanisms remain elusive. To clarify the role of lactic-acid-producing bacteria (LAB) on intestinal stem-cell (ISC)-mediated epithelial development, we fed mice with LAB-type symbionts such as Bifidobacterium and Lactobacillus spp. Here we show that administration of LAB-type symbionts significantly increased expansion of ISCs, Paneth cells, and goblet cells. Lactate stimulated ISC proliferation through Wnt/beta-catenin signals of Paneth cells and intestinal stromal cells. Moreover, Lactobacillus plantarum strains lacking lactate dehydrogenase activity, which are deficient in lactate production, elicited less ISC proliferation. Pre-treatment with LAB-type symbionts or lactate protected mice in response to gut injury provoked by combined treatments with radiation and a chemotherapy drug. Impaired ISC-mediated epithelial development was found in mice deficient of the lactate G-proteincoupled receptor, Gpr81. Our results demonstrate that LAB-type symbiont-derived lactate plays a pivotal role in promoting ISC-mediated epithelial development in a Gpr81-dependent manner.