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...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.展开更多
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 de...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.展开更多
Accumulating evidence revealed that some probiotics regulated lipid metabolism and alleviated diet-induced non-alcoholic fatty liver disease(NAFLD).This study mainly explored whether yogurt-derived Lactobacillus plant...Accumulating evidence revealed that some probiotics regulated lipid metabolism and alleviated diet-induced non-alcoholic fatty liver disease(NAFLD).This study mainly explored whether yogurt-derived Lactobacillus plantarum Q16 modulated lipid and energy metabolism,and suppressed microbial dysbiosis in high-fat diet(HFD)-fed mice.Results showed that oral administration of L.plantarum Q16 improved serum and hepatic lipid profile.Protein analysis showed that L.plantarum Q16 could reduce hepatic lipid content by reducing the expression of FAS,ACC,SCD-1,Srebp-lc and ATGL,but increasing expression levels of CPT-1α,PPAR-αand ATGL.Meanwhile,L.plantarum Q16 also improved hepatic energy metabolism by regulating FGF21/adiponectin/AMPKα/PGC-1αsignaling pathway.Metagenomic analysis also discovered that L.plantarum Q16 increased species diversity and richness of intestinal microbiota,promoted proliferation of beneficial commensals and suppressed the growth of endotoxin-producing microorganisms in the colon of HFD-fed mice.Overall,L.plantarum Q16 protected against HFD-induced NAFLD by improving hepatic profile and regulating colonic microbiota composition.展开更多
Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amylolique...Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.展开更多
Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin pr...Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin producer Streptomyces fradiae CGMCC 4.7387 from marine sediments,and the neomycin biosynthesis gene cluster was identified.Inactivation of the afsA-g gene encoding a γ-butyrolactone(GBL) synthase in S.fradiae CGMCC 4.7387 resulted in a significant decrease of neomycin production.Quantitative RT-PCR analysis revealed that the transcriptional level of neoR and the aphA-neoGH operon were reduced in the afsA-g::aac(3)Ⅳ mutant.Interestingly,a conserved binding site of AdpA,a key activator in the GBL regulatory cascade,was discovered upstream of neoR,a putative regulatory gene encoding a protein with an ATPase domain and a tetratricopeptide repeat domain.When neoR was inactivated,the neomycin production was reduced about 40%in comparison with the WT strain.Quantitative RT-PCR analysis revealed that the transcriptional levels of genes in the aphA-neoGH operon were reduced clearly in the neoR::aac(3)Ⅳ mutant.Finally,the titers of neomycin were improved considerably by overexpression of qfsA-gand neoR in S.fradiae CGMCC 4.7387.展开更多
基金Grant support was received from the National Natural Science Foundation of China(32072182).
文摘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.
基金the National Natural Science Foundation of China(32072182).
文摘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.
基金the financial support for this work provided by the National Natural Science Foundation of China(31771948&32072182)。
文摘Accumulating evidence revealed that some probiotics regulated lipid metabolism and alleviated diet-induced non-alcoholic fatty liver disease(NAFLD).This study mainly explored whether yogurt-derived Lactobacillus plantarum Q16 modulated lipid and energy metabolism,and suppressed microbial dysbiosis in high-fat diet(HFD)-fed mice.Results showed that oral administration of L.plantarum Q16 improved serum and hepatic lipid profile.Protein analysis showed that L.plantarum Q16 could reduce hepatic lipid content by reducing the expression of FAS,ACC,SCD-1,Srebp-lc and ATGL,but increasing expression levels of CPT-1α,PPAR-αand ATGL.Meanwhile,L.plantarum Q16 also improved hepatic energy metabolism by regulating FGF21/adiponectin/AMPKα/PGC-1αsignaling pathway.Metagenomic analysis also discovered that L.plantarum Q16 increased species diversity and richness of intestinal microbiota,promoted proliferation of beneficial commensals and suppressed the growth of endotoxin-producing microorganisms in the colon of HFD-fed mice.Overall,L.plantarum Q16 protected against HFD-induced NAFLD by improving hepatic profile and regulating colonic microbiota composition.
基金supported by the National Natural Science Foundation of China(32072182)。
文摘Type 2 diabetes mellitus(T2DM)is associated with liver dysfunction and intestinal dysbiosis.Bioactive peptides(BAPs)have been reported to ameliorate T2DM by preventing oxidative damage to the liver.Bacillus amyloliquefaciens fmb50 produces the lipopeptide surfactin with a wide range of biological activities.The effects of surfactin on T2DM,on the other hand,have not been studied.In the present study,80 mg/kg body weight surfactin supplementation lowered fasting blood glucose(FBG)levels by 21.05%and insulin resistance(IR)by 18.18%compared with those in the T2DM group,reduced inflammation,and increased antioxidant activity in mice with T2DM induced by a high-fat diet(HFD)and streptozotocin(STZ).According to further research,surfactin administration reduced Firmicutes-to-Bacteroidetes ratios while increasing Bifi dobacterium abundance by 20 times and the level of the tight junction protein Occludin by 18.38%and ZO-1 by 66.60%.Furthermore,surfactin also improved hepatic glucose metabolism by activating the adenosine monophosphate-activated protein kinase(AMPK)signalling pathway,increasing glycogen synthesis and glucose transporter 2(GLUT2)protein expression while reducing glucose-6-phosphatase(G6Pase)protein expression.In addition,the increased Bifi dobacterium abundance indirectly reduced the liver burden of the metabolic products indole,cresol and amine produced by saprophytic bacteria.All of these findings revealed that surfactin not only ameliorated HFD/STZ-induced gut dysbiosis and preserved intestinal barrier integrity but also enhanced hepatic glucose metabolism and detoxifi cation function in T2DM mice.The gut microbiota appeared to be important in controlling glucose metabolism,IR,fat accumulation,inflammation and antioxidation,according to Spearman’s correlation coeffi cients.All data indicated that surfactin alleviated hyperglycaemia in mice with T2DM induced by HFD/STZ.
基金funded in part by the Ministry of Science and Technology of China(2015CB150600)the National Natural Science Foundation of China(31370095 and 31522001)
文摘Neomycins are a group of aminoglycoside antibiotics with both clinical and agricultural applications.To elucidate the regulatory mechanism of neomycin biosynthesis,we completed draft genome sequencing of a neomycin producer Streptomyces fradiae CGMCC 4.7387 from marine sediments,and the neomycin biosynthesis gene cluster was identified.Inactivation of the afsA-g gene encoding a γ-butyrolactone(GBL) synthase in S.fradiae CGMCC 4.7387 resulted in a significant decrease of neomycin production.Quantitative RT-PCR analysis revealed that the transcriptional level of neoR and the aphA-neoGH operon were reduced in the afsA-g::aac(3)Ⅳ mutant.Interestingly,a conserved binding site of AdpA,a key activator in the GBL regulatory cascade,was discovered upstream of neoR,a putative regulatory gene encoding a protein with an ATPase domain and a tetratricopeptide repeat domain.When neoR was inactivated,the neomycin production was reduced about 40%in comparison with the WT strain.Quantitative RT-PCR analysis revealed that the transcriptional levels of genes in the aphA-neoGH operon were reduced clearly in the neoR::aac(3)Ⅳ mutant.Finally,the titers of neomycin were improved considerably by overexpression of qfsA-gand neoR in S.fradiae CGMCC 4.7387.