Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan.
Am J Physiol Renal Physiol. 2021 Oct 1;321(4):F455-F465. doi: 10.1152/ajprenal.00111.2021. Epub 2021 Aug 23.
Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion. Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to ischemia-reperfusion injury. This study aimed to determine the impact of antibiotic-induced microbiome depletion (AIMD) on renal glucose metabolism in mice. This is the first report confirming that AIMD is associated with decreased levels of pyruvate, a key intermediate in glucose metabolism, which may have been caused by activation of renal gluconeogenesis. We hypothesized that AIMD can increase the susceptibility of the kidney to ischemia-reperfusion injury.
最近的研究揭示了抗生素诱导的微生物组耗竭（AIMD）对宿主葡萄糖稳态的影响。肾脏在全身葡萄糖稳态中起着关键作用；然而，关于 AIMD 与肾脏葡萄糖代谢之间的关联的信息仍然有限。因此，我们旨在通过使用氨苄青霉素、万古霉素和左氧氟沙星组成的抗生素鸡尾酒（ABX）诱导肠道微生物组耗竭来确定 AIMD 对肾脏葡萄糖代谢的影响。结果表明，ABX 处理的小鼠的细菌 16s rRNA 表达、腔内容物短链脂肪酸和胆汁酸浓度以及血浆葡萄糖水平明显低于载体处理的小鼠。此外，ABX 处理显著降低了肾脏葡萄糖和丙酮酸水平。ABX 处理的小鼠肾脏皮质中葡萄糖-6-磷酸酶和磷酸烯醇丙酮酸羧激酶的 mRNA 表达水平明显高于载体处理的小鼠。我们进一步研究了 AIMD 对缺血性肾损伤后小鼠代谢状态改变的影响。暴露于缺血 60 分钟后，ABX 处理的小鼠肾脏丙酮酸浓度明显低于载体处理的小鼠。ABX 处理导致缺血再灌注后肾小管损伤更严重。我们的研究结果证实，AIMD 与肾脏中丙酮酸水平降低有关，这可能是由于肾脏糖异生的激活所致。因此，我们假设 AIMD 会增加肾脏对缺血再灌注损伤的易感性。本研究旨在确定抗生素诱导的微生物组耗竭（AIMD）对小鼠肾脏葡萄糖代谢的影响。这是首次证实 AIMD 与关键中间产物丙酮酸水平降低有关，这可能是由于肾脏糖异生的激活所致。我们假设 AIMD 可以增加肾脏对缺血再灌注损伤的易感性。
