BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human ...BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.展开更多
BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK...BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.展开更多
基金Supported by the University Scientific Research Projects of Anhui,No. KJ2020A0401 and 2022AH050491the open fund of the Ministry of Education Key Laboratory of Glucolipid Metabolic Disorder,No. GYDKFXM01+5 种基金the Anhui University Collaborative Innovation Project,No. GXXT-2020-025the National Natural Science Foundation of China,No. 82174153the National Key Research and Development Program,No. 2018YFC1704202the Anhui Provincial Quality Engineering Project of Universities,No. 2021jyxm0834the Major and Difficult Diseases Project of Anhui Province,No. 2021zdynjb06the Clinical Research Project of Anhui University of Traditional Chinese Medicine,No. 2021yfylc01
文摘BACKGROUND In recent years,the incidence of type 2 diabetes(T2DM)has shown a rapid growth trend.Goto Kakizaki(GK)rats are a valuable model for the study of T2DM and share common glucose metabolism features with human T2DM patients.A series of studies have indicated that T2DM is associated with the gut microbiota composition and gut metabolites.We aimed to systematically characterize the faecal gut microbes and metabolites of GK rats and analyse the relationship between glucose and insulin resistance.AIM To evaluate the gut microbial and metabolite alterations in GK rat faeces based on metagenomics and untargeted metabolomics.METHODS Ten GK rats(model group)and Wistar rats(control group)were observed for 10 wk,and various glucose-related indexes,mainly including weight,fasting blood glucose(FBG)and insulin levels,homeostasis model assessment of insulin resistance(HOMA-IR)and homeostasis model assessment ofβcell(HOMA-β)were assessed.The faecal gut microbiota was sequenced by metagenomics,and faecal metabolites were analysed by untargeted metabolomics.Multiple metabolic pathways were evaluated based on the differential metabolites identified,and the correlations between blood glucose and the gut microbiota and metabolites were analysed.RESULTS The model group displayed significant differences in weight,FBG and insulin levels,HOMA-IR and HOMA-βindexes(P<0.05,P<0.01)and a shift in the gut microbiota structure compared with the control group.The results demonstrated significantly decreased abundances of Prevotella sp.CAG:604 and Lactobacillus murinus(P<0.05)and a significantly increased abundance of Allobaculum stercoricanis(P<0.01)in the model group.A correlation analysis indicated that FBG and HOMA-IR were positively correlated with Allobaculum stercoricanis and negatively correlated with Lactobacillus murinus.An orthogonal partial least squares discriminant analysis suggested that the faecal metabolic profiles differed between the model and control groups.Fourteen potential metabolic biomarkers,including glycochenodeoxycholic acid,uric acid,13(S)-hydroxyoctadecadienoic acid(HODE),N-acetylaspartate,β-sitostenone,sphinganine,4-pyridoxic acid,and linoleic acid,were identified.Moreover,FBG and HOMA-IR were found to be positively correlated with glutathione,13(S)-HODE,uric acid,4-pyridoxic acid and allantoic acid and negatively correlated with 3-α,7-α,chenodeoxycholic acid glycine conjugate and 26-trihydroxy-5-β-cholestane(P<0.05,P<0.01).Allobaculum stercoricanis was positively correlated with linoleic acid and sphinganine(P<0.01),and 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate was negatively associated with Prevotella sp.CAG:604(P<0.01).The metabolic pathways showing the largest differences were arginine biosynthesis;primary bile acid biosynthesis;purine metabolism;linoleic acid metabolism;alanine,aspartate and glutamate metabolism;and nitrogen metabolism.CONCLUSION Metagenomics and untargeted metabolomics indicated that disordered compositions of gut microbes and metabolites may be common defects in GK rats.
基金National Natural Science Foundation of China,No.81603574 and No.81774286National Key Research and Development Program,No.2018YFC1704202 and No.2020YFE0201800+1 种基金University Scientific Research Projects of Anhui,No.KJ2020A0401 and No.KJ2019A0442Province Science Foundation of Anhui,No.1708085QH213.
文摘BACKGROUND A recent investigation showed that the prevalence of type 2 diabetes mellitus(T2DM)is 12.8%among individuals of Han ethnicity.Gut microbiota has been reported to play a central role in T2DM.Goto-Kakizaki(GK)rats show differences in gut microbiota compared to non-diabetic rats.Previous studies have indicated that berberine could be successfully used to manage T2DM.We sought to understand its hypoglycaemic effect and role in the regulation of the gut microbiota.AIM To determine whether berberine can regulate glucose metabolism in GK rats via the gut microbiota.METHODS GK rats were acclimatized for 1 wk.The GK rats were randomly divided into three groups and administered saline(Mo),metformin(Me),or berberine(Be).The observation time was 8 wk,and weight,fasting blood glucose(FBG),insulin,and glucagon-like peptide-1(GLP-1)were measured.Pancreatic tissue was observed for pathological changes.Additionally,we sequenced the 16S rRNA V3-V4 region of the gut microbiota and analysed the structure.RESULTS Compared with the Mo group,the Me and Be groups displayed significant differences in FBG(P<0.01)and GLP-1(P<0.05).A significant decrease in weight and homeostatic model assessment-insulin resistance was noted in the Be group compared with those in the Me group(P<0.01).The pancreatic islets of the Me-and Be-treated rats showed improvement in number,shape,and necrosis compared with those of Mo-treated rats.A total of 580 operational taxonomic units were obtained in the three groups.Compared to the Mo group,the Me and Be groups showed a shift in the structure of the gut microbiota.Correlation analysis indicated that FBG was strongly positively correlated with Clostridia_UCG-014(P<0.01)and negatively correlated with Allobaculum(P<0.01).Body weight showed a positive correlation with Desulfovibrionaceae(P<0.01)and a negative correlation with Akkermansia(P<0.01).Importantly,our results demonstrated that Me and Be could significantly decrease Bacteroidetes(P<0.01)and the Bacteroidetes/Firmicutes ratio(P<0.01).Furthermore,Muribaculaceae(P<0.01;P<0.05)was significantly decreased in the Me and Be groups,and Allobaculum(P<0.01)was significantly increased.CONCLUSION Berberine has a substantial effect in improving metabolic parameters and modulating the gut microbiota composition in T2DM rats.
