The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug–microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug–microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug–microbiota interactions.
{"title":"A new evaluation system for drug–microbiota interactions","authors":"Tian-Hao Liu, Chen-Yang Zhang, Hang Zhang, Jing Jin, Xue Li, Shi-Qiang Liang, Yu-Zheng Xue, Feng-Lai Yuan, Ya-Hong Zhou, Xiu-Wu Bian, Hong Wei","doi":"10.1002/imt2.199","DOIUrl":"10.1002/imt2.199","url":null,"abstract":"<p>The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug–microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug–microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug–microbiota interactions.</p>","PeriodicalId":73342,"journal":{"name":"iMeta","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/imt2.199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akkermansia muciniphila pretreatment mitigated Listeria monocytogenes infection in mice. A. muciniphila improved gut microbiota disturbed by L. monocytogenes infection and significantly increased the level of intestinal linoleic acid in mice. Linoleic acid strengthened the intestinal epithelial barrier and reduced pathogen translocation partly by regulating NF-κB/MLCK pathway in a GPR40-dependent manner.