Microorganisms including bacteria,viruses,protozoa,and fungi living in the gastrointestinal tract are collectively known as the gut microbiota.Dysbiosis is the imbalance in microbial composition on or inside the body ...Microorganisms including bacteria,viruses,protozoa,and fungi living in the gastrointestinal tract are collectively known as the gut microbiota.Dysbiosis is the imbalance in microbial composition on or inside the body relative to healthy state.Altered Firmicutes to Bacteroidetes ratio and decreased abundance of Akkermansia muciniphila are the predominant gut dysbiosis associated with the pathogenesis of type 2 diabetes mellitus(T2DM)and metabolic syndrome.Pathophysiological mechanisms linking gut dysbiosis,and metabolic diseases and their complications include altered metabolism of short-chain fatty acids and bile acids,interaction with gut hormones,increased gut microbial metabolite trimethylamine-N-oxide,bacterial translocation/Leaky gut syndrome,and endotoxin production such as lipopolysaccharides.The association between the gut microbiota and glycemic agents,however,is much less understood and is the growing focus of research and conversation.Recent studies suggest that the gut microbiota and anti-diabetic medications are interdependent on each other,meaning that while anti-diabetic medications alter the gut microbiota,the gut microbiota also alters the efficacy of anti-diabetic medications.With increasing evidence regarding the significance of gut microbiota,it is imperative to review the role of gut microbiota in the pathogenesis of T2DM.This review also discusses the interaction between gut microbiota and the various medications used in the treatment of T2DM.展开更多
The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospe...The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction,with the longest follow-up of 7 years.The concentrations of plasma TMAO and its precursors,namely,choline and carnitine,were determined by liquid chromatography-mass spectrometry,and the FMO3 E158K polymorphisms(rs2266782)were genotyped.The top tertile of plasma TMAO was associated with a significant increment in hazard ratio(HR)for the composite outcome of cardiovascular death or heart transplantation(HR=1.47,95%CI=1.13-1.91,P=0.004)compared with the lowest tertile.After adjustments of the potential confounders,higher TMAO could still be used to predict the risk of the primary endpoint(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).This result was also obtained after further adjustment for carnitine(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).The FM03 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort,and lower TMAO levels were found in the AA-genotype.Thus,higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders,and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.展开更多
文摘Microorganisms including bacteria,viruses,protozoa,and fungi living in the gastrointestinal tract are collectively known as the gut microbiota.Dysbiosis is the imbalance in microbial composition on or inside the body relative to healthy state.Altered Firmicutes to Bacteroidetes ratio and decreased abundance of Akkermansia muciniphila are the predominant gut dysbiosis associated with the pathogenesis of type 2 diabetes mellitus(T2DM)and metabolic syndrome.Pathophysiological mechanisms linking gut dysbiosis,and metabolic diseases and their complications include altered metabolism of short-chain fatty acids and bile acids,interaction with gut hormones,increased gut microbial metabolite trimethylamine-N-oxide,bacterial translocation/Leaky gut syndrome,and endotoxin production such as lipopolysaccharides.The association between the gut microbiota and glycemic agents,however,is much less understood and is the growing focus of research and conversation.Recent studies suggest that the gut microbiota and anti-diabetic medications are interdependent on each other,meaning that while anti-diabetic medications alter the gut microbiota,the gut microbiota also alters the efficacy of anti-diabetic medications.With increasing evidence regarding the significance of gut microbiota,it is imperative to review the role of gut microbiota in the pathogenesis of T2DM.This review also discusses the interaction between gut microbiota and the various medications used in the treatment of T2DM.
基金This work was supported by National Key R&D Program of China(Nos.2017YFC0909400 and 2017YFC1307700)Projects from National Natural Science Foundation of China(Nos.81630010,91639108,81770272,81873506,82070235,and 81790624)+3 种基金the Beijing Municipal Natural Science Foundation(No.7191013)China Postdoctoral Science Foundation(No.2020M680261)National Postdoctoral Program for Innovative Talents(No.BX20200022)Integrated Innovative Team for Human Disease Program of Tongji Medical College,HUST(No.2015ZDTD044).
文摘The association among plasma trimethylamine-N-oxide(TMAO),FMO3 polymorphisms,and chronic heart failure(CHF)remains to be elucidated.TMAO is a microbiota-dependent metabolite from dietary choline and carnitine.A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction,with the longest follow-up of 7 years.The concentrations of plasma TMAO and its precursors,namely,choline and carnitine,were determined by liquid chromatography-mass spectrometry,and the FMO3 E158K polymorphisms(rs2266782)were genotyped.The top tertile of plasma TMAO was associated with a significant increment in hazard ratio(HR)for the composite outcome of cardiovascular death or heart transplantation(HR=1.47,95%CI=1.13-1.91,P=0.004)compared with the lowest tertile.After adjustments of the potential confounders,higher TMAO could still be used to predict the risk of the primary endpoint(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).This result was also obtained after further adjustment for carnitine(adjusted HR=1.33,95%CI=1.01-1.74,P=0.039).The FM03 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort,and lower TMAO levels were found in the AA-genotype.Thus,higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders,and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.