Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China.
Department of Anesthesiology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China.
Redox Biol. 2024 Nov;77:103373. doi: 10.1016/j.redox.2024.103373. Epub 2024 Sep 27.
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.
肠道微生物组在急性肾损伤（AKI）中的作用正逐渐受到认识。研究表明，热量限制（CR）可增强啮齿动物肾脏对缺血/再灌注损伤的抵抗力。然而，尚不清楚肠道微生物群是否介导 CR 对缺血/再灌注引起的肾脏损伤（IRI）的保护作用。在此，我们表明 CR 改善了 IRI 引起的肾功能障碍、氧化应激、细胞凋亡和炎症，同时增强了肠道屏障功能。此外，肠道微生物群耗竭阻断了 CR 在 AKI 小鼠中的有益作用。16S rRNA 和代谢组学分析表明，CR 富集了肠道共生拟杆菌（Parabacteroides goldsteinii，P. goldsteinii）并上调了血清代谢物全氟戊烷的水平。P. goldsteinii 的肠道定植和全氟戊烷的口服给药在 AKI 小鼠中表现出与 CR 相似的有益作用。RNA 测序和实验数据表明，全氟戊烷通过拮抗氧化爆发和 NFκB 诱导的 NLRP3 炎性小体激活来保护 AKI 诱导的肾损伤。此外，我们筛选并发现 Hamaudol 通过促进 P. goldsteinii 的生长来改善肾功能不全。我们的研究结果揭示了肠道微生物群 P. goldsteinii 和血清代谢物全氟戊烷在 CR 对 AKI 的益处中的作用。
