Affiliation:
1. Zhujiang Hospital of Southern Medical University
2. School of Traditional Chinese Medicine, Southern Medical University
3. Dongguan Hospital of Guangzhou University of Chinese Medicine
4. School of Chinese Medicine, Hong Kong Baptist University
5. Nanfang Hospital of Southern Medical University
Abstract
Abstract
Background
The prevalence of hyperuricemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise, and it is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins as the critical mediators in the gut-kidney axis that cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role of microbiota in HUA-induced renal injury and the underlying mechanism reminds unknown.
Results
Uricase-knockout(UOX−/−) rats is a model of HUA exhibited renal function impairment, renal tubular injury, fibrosis, activation of NLRP3 inflammasome and compromised intestinal barrier functions. The 16S rRNA sequencing and function prediction revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. Metabolomic analysis further confirmed the increase of renal uremic toxins. To provide additional evidence, fecal microbiota transplantation (FMT) was conducted, where mice recolonized with HUA microbiota exhibited severe renal injury and compromised intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3-/-) I/R mice, the deleterious effects of HUA microbiota on renal injury and intestinal barrier were eliminated.
Conclusion
Our results demonstrate that HUA-induced gut dysbiosis promotes the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal disease by targeting the microbiota and NLRP3 inflammasome.
Publisher
Research Square Platform LLC