Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism.The gut microbiome,the collection of microorganisms in the gastrointestinal tract,can alter the metabolic outcome of pharma...Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism.The gut microbiome,the collection of microorganisms in the gastrointestinal tract,can alter the metabolic outcome of pharmaceuticals,environmental toxicants,and heavy metals,thereby changing their pharmacokinetics.Direct chemical modification of xenobiotics by the gut microbiome,either through the intestinal tract or re-entering the gut via enterohepatic circulation,can lead to increased metabolism or bioactivation,depending on the enzymatic activity within the microbial niche.Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways.Additionally,the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell-cell adhesion proteins,supporting the protective mucosal layer,and/or directly sequestering chemicals.Lastly,host gene expression is regulated by the microbiome,including CYP450s,multi-drug resistance proteins,and the transcription factors that regulate them.While the microbiome affects the host and pharmacokinetics of the xenobiotic,xenobiotics can also influence the viability and metabolism of the microbiome.Our understanding of the complex interconnectedness between host,microbiome,and metabolism will advance with new modeling systems,technology development and refinement,and mechanistic studies focused on the contribution of human and microbial metabolism.展开更多
Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advanta...Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease.In the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs.The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies.The use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions.Lipidomics combined with other“omics”has characterized lipid metabolism disorders in T2DM.The combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.展开更多
文摘Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism.The gut microbiome,the collection of microorganisms in the gastrointestinal tract,can alter the metabolic outcome of pharmaceuticals,environmental toxicants,and heavy metals,thereby changing their pharmacokinetics.Direct chemical modification of xenobiotics by the gut microbiome,either through the intestinal tract or re-entering the gut via enterohepatic circulation,can lead to increased metabolism or bioactivation,depending on the enzymatic activity within the microbial niche.Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways.Additionally,the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell-cell adhesion proteins,supporting the protective mucosal layer,and/or directly sequestering chemicals.Lastly,host gene expression is regulated by the microbiome,including CYP450s,multi-drug resistance proteins,and the transcription factors that regulate them.While the microbiome affects the host and pharmacokinetics of the xenobiotic,xenobiotics can also influence the viability and metabolism of the microbiome.Our understanding of the complex interconnectedness between host,microbiome,and metabolism will advance with new modeling systems,technology development and refinement,and mechanistic studies focused on the contribution of human and microbial metabolism.
基金Supported by Grant from International Joint Usage/Research Center,the Institute of Medical Science,the University of Tokyo,No.New-2020-K2012and Open Project of Shandong Provincial Key Laboratory of Infection and Immunity,No.2.
文摘Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease.In the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs.The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies.The use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions.Lipidomics combined with other“omics”has characterized lipid metabolism disorders in T2DM.The combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.
