The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

中文翻译：

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肠道微生物组和代谢物介导急性肾损伤后小鼠热量限制的益处


肠道微生物组在急性肾损伤 （AKI） 中的作用越来越受到认可。热量限制 （CR） 已被证明可以增强啮齿动物对肾脏缺血/再灌注损伤的抵抗力。尽管如此，尚不清楚肠道菌群是否介导了 CR 对肾脏缺血/再灌注诱导损伤 （IRI） 的保护。在此，我们表明 CR 改善了 IRI 引发的肾功能障碍、氧化应激、细胞凋亡和炎症，以及增强的肠道屏障功能。此外，肠道菌群耗竭阻断了 CR 对 AKI 小鼠的有利作用。16S rRNA 和代谢组学分析显示，CR 富集肠道共生副拟杆菌 goldsteinii （P. goldsteinii） 并上调血清代谢物十二氟戊坦水平。P. goldsteinii 的肠道定植和口服 dodecafluorpentan 在 AKI 小鼠中显示出与 CR 相似的有益作用。RNA 测序和实验数据显示，十二氟戊坦通过拮抗氧化爆发和 NFκB 诱导的 NLRP3 炎性小体激活来防止 AKI 诱导的肾损伤。此外，我们筛选发现 Hamaudol 通过促进 P. goldsteinii 的生长来改善肾功能不全。我们的结果揭示了肠道微生物群 P. goldsteinii 和血清代谢物 dodecafluorpentan 在 CR 对 AKI 的益处中的作用。