BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,...BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.展开更多
BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We sear...BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.展开更多
In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with wh...In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with whole egg group(WE),HFD with free-yolk egg substitute group(YFES),and HFD with lovastatin group(Lov).Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum.It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight,low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC),while increasing high-density lipoprotein cholesterol.YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids,while decreasing phosphatidylinositol than WE.A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out.Carnitine C18:2 and C12:1,SM(d18:0/12:0),and SM(d18:1/14:1)were significantly upregulated in YFES compared to WE.YFES reduced expression of SREBP-1c and Cpt1a,while did not affect the expression of PPAR-α.Sphingomyelin biomarkers were positively related to the TC(|r|>0.6),while PPAR-αwas negatively correlated with triglyceride and LDL-C levels.To sum up,YFES attenuated HFD-induced Met S by improving the serum phospholipids,which account for its modulation of glycerophospholipid metabolism.展开更多
Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,an...Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.展开更多
Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied...Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.展开更多
Sugarcane leaves-derived polyphenols(SLP)have been demonstrated to have diverse health-promoting benefits,but the mechanism of action has not been fully elucidated.This study aimed to investigate the anti-metabolic di...Sugarcane leaves-derived polyphenols(SLP)have been demonstrated to have diverse health-promoting benefits,but the mechanism of action has not been fully elucidated.This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice.In the current study,we prepared the SLP mainly consisting of three flavonoid glycosides,three phenol derivatives,and two lignans including one new compound,and further demonstrated that SLP reduced body weight gain and fat accumulation,improved glucose and lipid metabolism disorders,ameliorated hepatic steatosis,and regulated short-chain fatty acids(SCFAs)production and secondary bile acids metabolism in ob/ob mice.Notably,SLP largely altered the gut microbiota composition,especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens.Oral gavage with the above two strains ameliorated metabolic syndrome(MetS),regulated secondary bile acid metabolism,and increased the production of SCFAs in high-fat diet(HFD)-induced obese mice.These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.展开更多
The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndr...The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.展开更多
Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on...Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.展开更多
基金supported by the National Natural Science Foundation of China(82172182 and 82102311)Natural Science Foundation of Jiangsu Province(BK20211136)+2 种基金China Postdoctoral Science Foundation(2018M643890 and 2020M683718)Xuzhou Science and Technology Project(KC21215 and KC22136)Development Fund Project of Affiliated Hospital of Xuzhou Medical University(XYFY202232)。
文摘BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.
基金supported by grants from the National Natural Science Foundation of China (82370378 and 82070388)Taishan Scholar Program of Shandong Province (tsqn202211310)National Natural Science Foundation of Shandong Province (ZR2020MH035)。
文摘BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.
基金supported by the Applied Basic Research of Shanxi Province(201901D211381)the Innovation-driven Development Capacity Enhancement Fund of Shanxi Province(SXYBKY2019041)+2 种基金National Key Research and Development Program(2021YFD1600604-03)Shanxi Scholarship Council of China(2021-068)Shanxi Agricultural University High-Level Talent Project(2021XG013)。
文摘In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with whole egg group(WE),HFD with free-yolk egg substitute group(YFES),and HFD with lovastatin group(Lov).Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum.It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight,low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC),while increasing high-density lipoprotein cholesterol.YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids,while decreasing phosphatidylinositol than WE.A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out.Carnitine C18:2 and C12:1,SM(d18:0/12:0),and SM(d18:1/14:1)were significantly upregulated in YFES compared to WE.YFES reduced expression of SREBP-1c and Cpt1a,while did not affect the expression of PPAR-α.Sphingomyelin biomarkers were positively related to the TC(|r|>0.6),while PPAR-αwas negatively correlated with triglyceride and LDL-C levels.To sum up,YFES attenuated HFD-induced Met S by improving the serum phospholipids,which account for its modulation of glycerophospholipid metabolism.
基金funded by the National Natural Science Foundation of China(No.32170788)National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-023)Beijing Natural Science Foundation(No.7232123).
文摘Objective To assess the diagnostic accuracy of bowel sound analysis for irritable bowel syndrome(IBS)with a systematic review and meta-analysis.Methods We searched MEDLINE,Embase,the Cochrane Library,Web of Science,and IEEE Xplore databases until September 2023.Cross-sectional and case-control studies on diagnostic accuracy of bowel sound analysis for IBS were identified.We estimated the pooled sensitivity,specificity,positive likelihood ratio,negative likeli-hood ratio,and diagnostic odds ratio with a 95% confidence interval(CI),and plotted a summary receiver operat-ing characteristic curve and evaluated the area under the curve.Results Four studies were included.The pooled diagnostic sensitivity,specificity,positive likelihood ratio,nega-tive likelihood ratio,and diagnostic odds ratio were 0.94(95%CI,0.87‒0.97),0.89(95%CI,0.81‒0.94),8.43(95%CI,4.81‒14.78),0.07(95%CI,0.03‒0.15),and 118.86(95%CI,44.18‒319.75),respectively,with an area under the curve of 0.97(95%CI,0.95‒0.98).Conclusions Computerized bowel sound analysis is a promising tool for IBS.However,limited high-quality data make the results'validity and applicability questionable.There is a need for more diagnostic test accuracy studies and better wearable devices for monitoring and analysis of IBS.
基金supported by the shanghai agriculture applied technology development program(2019-02-08-00-07-F01152)the national science fund for distinguished young scholars(32025029)+1 种基金the shanghai engineering research center of food microbiology program(19DZ2281100)the national key R&D program of china(2018YFC1604305)。
文摘Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.
基金supported by the National key research and development program of China(2019YFA0905600)the Science and Technology Service Network Program of the Chinese Academy of Sciences(KFJ-STS-QYZD-201-5-3)the Strategic Priority Research Program(Class B)of Chinese Academy of Sciences(XDB 38020300)。
文摘Sugarcane leaves-derived polyphenols(SLP)have been demonstrated to have diverse health-promoting benefits,but the mechanism of action has not been fully elucidated.This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice.In the current study,we prepared the SLP mainly consisting of three flavonoid glycosides,three phenol derivatives,and two lignans including one new compound,and further demonstrated that SLP reduced body weight gain and fat accumulation,improved glucose and lipid metabolism disorders,ameliorated hepatic steatosis,and regulated short-chain fatty acids(SCFAs)production and secondary bile acids metabolism in ob/ob mice.Notably,SLP largely altered the gut microbiota composition,especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens.Oral gavage with the above two strains ameliorated metabolic syndrome(MetS),regulated secondary bile acid metabolism,and increased the production of SCFAs in high-fat diet(HFD)-induced obese mice.These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20200084)the National Natural Science Foundation of China(31871773 and 31820103010)+1 种基金the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province and Key Talents Project of“Strengthening Health through Science and Education”of Wuxi Health and Family Planning Commission(ZDRC039)Top Talents Project of“Six-one Project”for High-level Health Talents in Jiangsu Province(LGY2018016)。
文摘The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.
基金supported by National Natural Science Foundation of China(32270420,32072220)National Key Research and Development Project(2020YFD1001405)+2 种基金Shanxi Province Science Foundation(202103021224011)Shanxi Key Laboratory for Research and Development of Regional PlantsShanxi Province“136”Revitalization Medical Project Construction Funds。
文摘Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota homeostasis.Metabolites derived from gut microbes play essential roles in Met S prevention and therapy.Here,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of EMBP.The obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP treatment.The protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier function.Using microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides acidifaciens.The fecal microbiota transplantation(FMT)also demonstrated this phenomenon.In addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S mice.Notably,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by EMBP.In addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met S.The results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.
