Lacticaseibacillus rhamnosus Fmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition

Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.

Ameliorative effect of Lacticaseibacillus rhamnosus Fmb14 from Chinese yogurt on hyperuricemia

Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.