The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease

• Published in: Cell metabolism Vol. 33; no. 10; pp. 1926 - 1942.e8
• Main Authors: Zhu, Han, Cao, Chujin, Wu, Zhongcai, Zhang, Heping, Sun, Zhihong, Wang, Meng, Xu, Huzi, Zhao, Zhi, Wang, Yuxi, Pei, Guangchang, Yang, Qian, Zhu, Fengming, Yang, Juan, Deng, Xuan, Hong, Yu, Li, Yinzheng, Sun, Jie, Zhu, Fan, Shi, Mengxia, Qian, Kun, Ye, Ting, Zuo, Xuezhi, Zhao, Fenfei, Guo, Jing, Xu, Gang, Yao, Ying, Zeng, Rui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.10.2021
• Subjects: acute kidney injury; Animals; chronic kidney disease; Dysbiosis; Fatty Acids, Volatile - metabolism; gut microbiota; Lactobacillus casei - metabolism; Lactobacillus casei Zhang; Mice; nicotinamide; Probiotics - therapeutic use; Renal Insufficiency, Chronic; short-chain fatty acids; Lactobacillus casei Zhang; chronic kidney disease; acute kidney injury; short-chain fatty acids; gut microbiota; nicotinamide
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2021.06.014

The relationship between gut microbial dysbiosis and acute or chronic kidney disease (CKD) is still unclear. Here, we show that oral administration of the probiotic Lactobacillus casei Zhang (L. casei Zhang) corrected bilateral renal ischemia-reperfusion (I/R)-induced gut microbial dysbiosis, alleviated kidney injury, and delayed its progression to CKD in mice. L. casei Zhang elevated the levels of short-chain fatty acids (SCFAs) and nicotinamide in the serum and kidney, resulting in reduced renal inflammation and damage to renal tubular epithelial cells. We also performed a 1-year phase 1 placebo-controlled study of oral L. casei Zhang use (Chinese clinical trial registry, ChiCTR-INR-17013952), which was well tolerated and slowed the decline of kidney function in individuals with stage 3–5 CKD. These results show that oral administration of L. casei Zhang, by altering SCFAs and nicotinamide metabolism, is a potential therapy to mitigate kidney injury and slow the progression of renal decline. [Display omitted] •L. casei Zhang improves renal function and pathology in mouse models of AKI and CKD•L. casei Zhang ameliorates gut microbial dysbiosis in both AKI and CKD•L. casei Zhang reduces renal inflammation and damage via SCFAs and nicotinamide•L. casei Zhang slows the decline of kidney function in individuals with stage 3–5 CKD Zhu et al. demonstrate that the probiotic L. casei Zhang slows kidney disease progression in mouse models and individuals with chronic kidney disease (CKD) through increasing the levels of short-chain fatty acids and via nicotinamide metabolism, which together modulate the inflammatory response of local macrophages and tubular epithelia cells. These findings suggest a potential therapeutic approach for acute kidney injury and CKD.