Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice.
Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice.
复制标题
抗生素诱导的微生物组耗竭会改变小鼠肾葡萄糖代谢，并加剧小鼠缺血再灌注损伤后的肾损伤。
DOI：
10.1152/ajprenal.00111.2021
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Matsubara K.
中科院分区：
文献类型：
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作者：
Osada Y;Nakagawa S;Ishibe K;Takao S;Shimazaki A;Itohara K;Imai S;Yonezawa A;Nakagawa T;Matsubara K.
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发挥着关键作用;然而，有关AIMD与肾脏葡萄糖代谢之间关系的信息仍然有限。因此，我们旨在通过使用由氨苄青霉素、万古霉素和左氧氟沙星组成的抗生素鸡尾酒（ABX）诱导小鼠肠道微生物组耗竭来确定AIMD对肾脏葡萄糖代谢的影响。结果显示，ABX处理的小鼠中细菌16 s rRNA表达、短链脂肪酸和胆汁酸的管腔浓度以及血糖水平显著低于溶剂处理的小鼠。此外，ABX治疗显著降低肾脏葡萄糖和丙酮酸水平。ABX处理的小鼠肾皮质中葡萄糖-6-磷酸酶和磷酸烯醇式丙酮酸羧激酶的mRNA表达水平显著高于溶剂处理的小鼠。我们进一步研究了AIMD对缺血诱导肾损伤后小鼠代谢状态改变的影响。暴露于缺血60分钟后，肾脏丙酮酸浓度显着低于ABX处理的小鼠比溶剂处理的小鼠。ABX治疗引起更严重的缺血再灌注后的肾小管损伤。我们的研究结果证实，AIMD与肾脏中丙酮酸水平降低相关，这可能是由肾脏新生血管激活引起的。因此，我们假设AIMD会增加肾脏对缺血再灌注损伤的脆弱性。新&值得注意的是这项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。这是第一份确认AIMD与丙酮酸水平降低相关的报告，丙酮酸是葡萄糖代谢的关键中间体，可能是由肾脏再生激活引起的。我们假设AIMD可增加肾脏对缺血再灌注损伤的易感性。
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.NEW & NOTEWORTHYThis 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.