Toronto General Hospital Research Institute, UHN, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Toronto General Hospital Research Institute, UHN, Toronto, ON M5G 1L7, Canada.
Cell Metab. 2018 Jan 9;27(1):101-117.e5. doi: 10.1016/j.cmet.2017.09.019. Epub 2017 Oct 19.
The gut microbiota alters energy homeostasis. In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown. Here we report that upper small intestinal glucose sensing triggers an SGLT1-dependent pathway to lower glucose production in rodents. High-fat diet (HFD) feeding reduces glucose sensing and SGLT1 expression in the upper small intestine. Upper small intestinal metformin treatment restores SGLT1 expression and glucose sensing while shifting the upper small intestinal microbiota partly by increasing the abundance of Lactobacillus. Transplantation of upper small intestinal microbiota from metformin-treated HFD rats to the upper small intestine of untreated HFD rats also increases the upper small intestinal abundance of Lactobacillus and glucose sensing via an upregulation of SGLT1 expression. Thus, we demonstrate that metformin alters upper small intestinal microbiota and impacts a glucose-SGLT1-sensing glucoregulatory pathway.
肠道微生物群改变能量平衡。与此同时，二甲双胍调节小肠上部的钠-葡萄糖共转运蛋白 1（SGLT1），但尚不清楚是微生物群的变化还是小肠上部的 SGLT1 依赖性途径介导了二甲双胍的作用。在这里，我们报告称，小肠上部的葡萄糖感应会触发一种 SGLT1 依赖性途径，以降低啮齿动物的葡萄糖生成。高脂肪饮食（HFD）喂养会降低小肠上部的葡萄糖感应和 SGLT1 表达。小肠上部的二甲双胍治疗可恢复 SGLT1 表达和葡萄糖感应，同时通过增加乳酸杆菌的丰度部分改变小肠上部的微生物群。将来自接受二甲双胍治疗的 HFD 大鼠的小肠上部微生物群移植到未接受治疗的 HFD 大鼠的小肠上部，也可通过上调 SGLT1 表达来增加小肠上部的乳酸杆菌丰度和葡萄糖感应。因此，我们证明了二甲双胍改变了小肠上部的微生物群，并影响了葡萄糖-SGLT1-感应的血糖调节途径。
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