Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury
Xue-Xue Zhu,
Xiao Fu,
Xin-Yu Meng,
Jia-Bao Su,
Guan-Li Zheng,
An-Jing Xu,
Guo Chen,
Yuan Zhang,
Yao Liu,
Xiao-Hui Hou,
Hong-Bo Qiu,
Qing-Yi Sun,
Jin-Yi Hu,
Zhuo-Lin Lv,
Yao Wang,
Hai-Bin Jiang,
Neng Bao,
Zhi-Jun Han,
Qing-Bo Lu,
Hai-Jian Sun
Affiliations
Xue-Xue Zhu
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Xiao Fu
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Xin-Yu Meng
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Jia-Bao Su
Department of Anesthesiology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Guan-Li Zheng
Department of Anesthesiology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
An-Jing Xu
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Guo Chen
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Yuan Zhang
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Yao Liu
Department of Ultrasound, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China
Xiao-Hui Hou
Department of Ultrasound, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, China
Hong-Bo Qiu
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Qing-Yi Sun
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Jin-Yi Hu
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Zhuo-Lin Lv
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Yao Wang
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China
Hai-Bin Jiang
Department of Cardiology, Wuxi No.2 People's Hospital (Jiangnan University Medical Center), Wuxi, Jiangsu, China
Neng Bao
Department of Nephrology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China; Corresponding author.
Zhi-Jun Han
Department of Clinical Research Center, Jiangnan University Medical Center (Wuxi No.2 People’s Hospital), Wuxi School of Medicine, Jiangnan University, Wuxi, China; Corresponding author.
Qing-Bo Lu
Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China; Corresponding author.
Hai-Jian Sun
Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China; Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China; Corresponding author. Wuxi School of Medicine, Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, 214122, China.
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.
