Combined administration of Lactiplantibacillus plantarum KLDS 1.0328 and puerarin alleviates high-fructose diet-induced hyperuricemia and cognitive impairment in mice

Combined L. plantarum and PUE attenuated HFrD-induced HUA and cognitive impairment. • Combined intervention lowered serum UA, hepatic XOD, and renal urate transporters. • Combined intervention increased PSD95/BDNF and ERK/CREB phosphorylation in brain. • The combination attenuated cecal microbiota alterations and colonic injury. Hyperuricemia (HUA) is a common metabolic disorder, which poses a threat to human health. This study examined the impact of Lactiplantibacillus plantarum KLDS 1.0328 (LP) in combination with puerarin (PUE) on high-fructose diet (HFrD)-induced HUA and associated cognitive impairment. Following the combined intervention, the levels of serum creatinine (CRE), blood urea nitrogen (BUN) and uric acid (UA) were decreased, while pathological damage, inflammatory responses, and oxidative stress in the kidney were alleviated. Moreover, the combined intervention reduced hepatic xanthine oxidase (XOD) activity and renal glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) protein expression. Notably, cognitive function was ameliorated in behavioral assessments. Furthermore, this intervention attenuated neuroinflammation and oxidative stress in brain tissues, while Synapsin I and postsynaptic density protein 95 (PSD95) expression, extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) phosphorylation, and brain-derived neurotrophic factor (BDNF) expression were increased in the LP + PUE-4 group. Additionally, the HFrD-induced gut microbiota dysbiosis was partially alleviated, particularly by shifting the Firmicutes/Bacteroidota ratio and modulating specific bacterial genera. Collectively, these findings indicated that the combined administration of L. plantarum KLDS 1.0328 and PUE attenuated HFrD-induced HUA and associated cognitive impairment when initiated concurrently with HFrD feeding. Download: Download high-res image (339KB) Download: Download full-size image