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 ofLactobacillus. 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 ofLactobacillusand 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.

中文翻译：

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二甲双胍可改变影响葡萄糖SGLT1的Glucoregulatory通路的上小肠菌群。

肠道菌群改变能量稳态。同时，二甲双胍调节上小肠钠葡萄糖共转运蛋白1（SGLT1），但尚不清楚上小肠中微生物群或SGLT1依赖性途径的变化介导二甲双胍的作用。在这里，我们报告说，小肠上部的葡萄糖感应触发了SGLT1依赖性途径，从而降低了啮齿动物的葡萄糖产生。高脂饮食（HFD）喂养会减少上小肠的葡萄糖感测和SGLT1表达。上小肠二甲双胍治疗可恢复SGLT1表达和葡萄糖感测，同时部分地通过增加乳酸杆菌的丰度来转移上小肠微生物群。将二甲双胍治疗的HFD大鼠的上部小肠菌群移植到未经治疗的HFD大鼠的上部小肠，也通过上调SGLT1表达而增加了乳酸杆菌的上部小肠丰度和葡萄糖感测。因此，我们证明二甲双胍改变了上部小肠菌群并影响了葡萄糖-SGLT1传感的糖调节途径。