High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We dem...High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.展开更多
A polyphenolic alkaloid-enriched extract(PAE)was prepared from the fruiting bodies of a wild edible mushroom Sarcodon leucopus.Oral administration of PAE reduced hyperglycemia,hyperlipidemia,hepatic steatosis,and LPS-...A polyphenolic alkaloid-enriched extract(PAE)was prepared from the fruiting bodies of a wild edible mushroom Sarcodon leucopus.Oral administration of PAE reduced hyperglycemia,hyperlipidemia,hepatic steatosis,and LPS-related infl ammation in high fat diet-induced obese(DIO)mice.Furthermore,we show that PAE produces taxonomic and predicted functional changes in the gut microbiome of DIO mice.A signifi cant decrease in the family of Ruminococcaceae,especially the secondary bile acid-producing bacteria of Intestinimonas and Anaerotruncus,is detected in the gut microbiome of PAE-treate mice.Accordingly,reductions of deoxycholic acid and lithocholic acid are found in the feces of PAE-treated DIO mice,which benefi ts for the intestinal integrity and the reduction of infl ammation.A gut microbiota related mechanism for the anti-metabolic syndrome effects of the PAE is proposed.We suppose the polyphenolic alkaloid extract from S.leucopus be a new and benefi cial prebiotic regulating glucose and lipid metabolisms.展开更多
AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples...AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.展开更多
Background:Vasovagal syncope(VVS)is common in children and greatly affect both physical and mental health.But the mechanisms have not been completely explained.This study was designed to analyze the gut microbiota in ...Background:Vasovagal syncope(VVS)is common in children and greatly affect both physical and mental health.But the mechanisms have not been completely explained.This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance.Methods:Fecal samples from 20 VVS children and 20 matched controls were collected,and the microbiota were analyzed by 16S rRNA gene sequencing.The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test.The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test.Results:No significant differences in diversity were evident between VVS and controls(P>0.05).At the family level,the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls(median[Q1,Q3]:22.10%[16.89%,27.36%]vs.13.92%[10.31%,20.18%],Z=-2.40,P<0.05),and LEfSe analysis revealed Ruminococcaceae as a discriminative feature(linear discriminant analysis[LDA]score>4,P<0.05).The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope(r=0.616,P<0.01).In terms of its correlation with hemodynamics,we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test(HUTT;r=-0.489 and-0.448,all P<0.05),but was positively correlated with the mean pressure drop and decline rate(r=0.489 and 0.467,all P<0.05)as well as diastolic pressure drop and decline rate at the HUTT positive response(r=0.579 and 0.589,all P<0.01)in VVS patients.Conclusion:Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS,suggesting that gut microbiota might be involved in the development of VVS.展开更多
Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the patho...Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota.The purpose of our study was to explore the features of gut microbiota in patients with AN,hoping to provide valuable information on its pathogenesis and treatment.Methods:In this cross-sectional study,from August 2020 to June 2021,patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital(n=30)were recruited as the AN group,and healthy controls(HC)were recruited from a middle school and a university in Beijing(n=30).Demographic data,Hamilton Depression Scale(HAMD)scores of the two groups,and length of stay of the AN group were recorded.Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA(rRNA)gene sequencing.Results:The weight(AN vs.HC,[39.31±7.90]kg vs.[56.47±8.88]kg,P<0.001)and body mass index(BMI,AN vs.HC,[14.92±2.54]kg/m^(2)vs.[20.89±2.14]kg/m^(2),P<0.001)of patients with AN were statistically significantly lower than those of HC,and HAMD scores in AN group were statistically significantly higher than those of HC.For alpha diversity,there were no statistically significant differences between the two groups;for beta diversity,the two groups differed obviously regarding community composition.Compared to HC,the proportion of Lachnospiraceae in patients with AN was statistically significantly higher(AN vs.HC,40.50%vs.31.21%,Z=-1.981,P=0.048),while that of Ruminococcaceae was lower(AN vs.HC,12.17%vs.19.15%,Z=-2.728,P=0.007);the proportion of Faecalibacterium(AN vs.HC,3.97%vs.9.40%,Z=-3.638,P<0.001)and Subdoligranulum(AN vs.HC,4.60%vs.7.02%,Z=-2.369,P=0.018)were statistically significantly lower,while that of Eubacterium_halli_group was significantly higher(AN vs.HC,7.63%vs.3.43%,Z=-2.115,P=0.035).Linear discriminant effect(LEfSe)analysis(LDA score>3.5)showed that o_Lachnospirales,f_Lachnospiraceae,and g_Eubacterium_halli_group(o,f andg represents order,family and genus respectively)were enriched in patients with AN.Microbial function of nutrient transport and metabolism in AN group were more abundant(P>0.05).In AN group,weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides,while positively correlated with Subdoligranulum.BMI was significantly positively correlated with Firmicutes;HAMD scores were significantly negatively correlated with Faecalibacterium.Conclusions:The composition of gut microbiota in patients with AN was different from that of healthy people.Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Natural Science Foundation of China(32272364)Shanghai Engineering Research Center of food microbiology program(19DZ2281100).
文摘High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.
基金This study was supported by the Project of Science and Technology Department of Tibet(XZ201901-GB-19).
文摘A polyphenolic alkaloid-enriched extract(PAE)was prepared from the fruiting bodies of a wild edible mushroom Sarcodon leucopus.Oral administration of PAE reduced hyperglycemia,hyperlipidemia,hepatic steatosis,and LPS-related infl ammation in high fat diet-induced obese(DIO)mice.Furthermore,we show that PAE produces taxonomic and predicted functional changes in the gut microbiome of DIO mice.A signifi cant decrease in the family of Ruminococcaceae,especially the secondary bile acid-producing bacteria of Intestinimonas and Anaerotruncus,is detected in the gut microbiome of PAE-treate mice.Accordingly,reductions of deoxycholic acid and lithocholic acid are found in the feces of PAE-treated DIO mice,which benefi ts for the intestinal integrity and the reduction of infl ammation.A gut microbiota related mechanism for the anti-metabolic syndrome effects of the PAE is proposed.We suppose the polyphenolic alkaloid extract from S.leucopus be a new and benefi cial prebiotic regulating glucose and lipid metabolisms.
文摘AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.
基金supported by a grant from the NationalYouth Top-notch Talent Support Program,Clinical Scientists Program of Peking University and Beijing Scienceand Technology Program(No.Z171100001017253).
文摘Background:Vasovagal syncope(VVS)is common in children and greatly affect both physical and mental health.But the mechanisms have not been completely explained.This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance.Methods:Fecal samples from 20 VVS children and 20 matched controls were collected,and the microbiota were analyzed by 16S rRNA gene sequencing.The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test.The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test.Results:No significant differences in diversity were evident between VVS and controls(P>0.05).At the family level,the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls(median[Q1,Q3]:22.10%[16.89%,27.36%]vs.13.92%[10.31%,20.18%],Z=-2.40,P<0.05),and LEfSe analysis revealed Ruminococcaceae as a discriminative feature(linear discriminant analysis[LDA]score>4,P<0.05).The relative abundance of Ruminococcaceae in VVS patients was positively correlated with the frequency of syncope(r=0.616,P<0.01).In terms of its correlation with hemodynamics,we showed that relative abundance of Ruminococcaceae was negatively correlated with the systolic and diastolic pressure reduction at the positive response in head-up tilt test(HUTT;r=-0.489 and-0.448,all P<0.05),but was positively correlated with the mean pressure drop and decline rate(r=0.489 and 0.467,all P<0.05)as well as diastolic pressure drop and decline rate at the HUTT positive response(r=0.579 and 0.589,all P<0.01)in VVS patients.Conclusion:Ruminococcaceae was the predominant gut bacteria and was associated with the clinical symptoms and hemodynamics of VVS,suggesting that gut microbiota might be involved in the development of VVS.
基金funded by the Cross Seed Fund of Peking University(No.A74479-01).
文摘Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota.The purpose of our study was to explore the features of gut microbiota in patients with AN,hoping to provide valuable information on its pathogenesis and treatment.Methods:In this cross-sectional study,from August 2020 to June 2021,patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital(n=30)were recruited as the AN group,and healthy controls(HC)were recruited from a middle school and a university in Beijing(n=30).Demographic data,Hamilton Depression Scale(HAMD)scores of the two groups,and length of stay of the AN group were recorded.Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA(rRNA)gene sequencing.Results:The weight(AN vs.HC,[39.31±7.90]kg vs.[56.47±8.88]kg,P<0.001)and body mass index(BMI,AN vs.HC,[14.92±2.54]kg/m^(2)vs.[20.89±2.14]kg/m^(2),P<0.001)of patients with AN were statistically significantly lower than those of HC,and HAMD scores in AN group were statistically significantly higher than those of HC.For alpha diversity,there were no statistically significant differences between the two groups;for beta diversity,the two groups differed obviously regarding community composition.Compared to HC,the proportion of Lachnospiraceae in patients with AN was statistically significantly higher(AN vs.HC,40.50%vs.31.21%,Z=-1.981,P=0.048),while that of Ruminococcaceae was lower(AN vs.HC,12.17%vs.19.15%,Z=-2.728,P=0.007);the proportion of Faecalibacterium(AN vs.HC,3.97%vs.9.40%,Z=-3.638,P<0.001)and Subdoligranulum(AN vs.HC,4.60%vs.7.02%,Z=-2.369,P=0.018)were statistically significantly lower,while that of Eubacterium_halli_group was significantly higher(AN vs.HC,7.63%vs.3.43%,Z=-2.115,P=0.035).Linear discriminant effect(LEfSe)analysis(LDA score>3.5)showed that o_Lachnospirales,f_Lachnospiraceae,and g_Eubacterium_halli_group(o,f andg represents order,family and genus respectively)were enriched in patients with AN.Microbial function of nutrient transport and metabolism in AN group were more abundant(P>0.05).In AN group,weight and BMI were significantly negatively correlated with the abundance of Bacteroidota and Bacteroides,while positively correlated with Subdoligranulum.BMI was significantly positively correlated with Firmicutes;HAMD scores were significantly negatively correlated with Faecalibacterium.Conclusions:The composition of gut microbiota in patients with AN was different from that of healthy people.Clinical indicators have correlations with the abundance of gut microbiota in patients with AN.
