Immunology Research Center, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan.
Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan.
Cell Rep. 2021 Nov 23;37(8):110016. doi: 10.1016/j.celrep.2021.110016.
Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.
增强肠道上皮屏障是管理与肠道微生物群相关疾病的一种潜在策略。在这里，我们证明双重特异性磷酸酶 6（Dusp6）基因敲除可增强结肠基础屏障完整性并改善葡聚糖硫酸钠（DSS）诱导的结肠损伤。Caco-2 细胞中的 DUSP6 突变增强了上皮特征，并增加了线粒体耗氧量，同时伴有葡萄糖代谢改变和糖酵解减少。我们发现 Dusp6 基因敲除小鼠对 DSS 诱导的菌群失调更具抵抗力，共笼和粪便微生物群移植实验表明，源自 Dusp6 基因敲除小鼠的肠道/粪便微生物群也能防止结肠炎。进一步的培养组学和单殖民地化实验表明，邓肯氏菌属中的一个肠道微生物群成员可赋予宿主对 DSS 诱导损伤的保护作用。我们确定 Dusp6 缺乏有利于塑造对防止与肠道屏障相关疾病相关的肠道微生物群生态平衡是有益的。
