A new evaluation system for drug–microbiota interactions

• Published in: iMeta 2024-06, Vol.3 (3), p.e199-n/a
• Main Authors: Liu, Tian‐Hao, Zhang, Chen‐Yang, Zhang, Hang, Jin, Jing, Li, Xue, Liang, Shi‐Qiang, Xue, Yu‐Zheng, Yuan, Feng‐Lai, Zhou, Ya‐Hong, Bian, Xiu‐Wu, Wei, Hong
• Format: Article
• Language: English
• Subjects: drug metabolism; drug–microbiota interactions; genetic and environmental factors; gut microbiota
• ISSN: 2770-596X; 2770-5986; 2770-596X
• DOI: 10.1002/imt2.199

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. Here, we propose a new evaluation system and research strategy for drug microbial interaction. Leveraging precision germ‐free animal models for the design of next‐generation drug active/toxic ingredients involving gut microbiota, as well as microbes sorting and cultromics, to elucidate the exact mechanism of interaction between single microbe and single drug ingredient in vivo. Highlights Shaped by both genetic and environmental factors, gut microbiota significantly influences the host's drug absorption, distribution, metabolism, and excretion (ADME) microenvironment, highlighting the need for a new evaluation system for drug‐microbiome interactions. To investigate the intricate nature of interactions between gut microbiota and drugs in vivo, a novel top‐down research approach utilizing germ‐free animal models is proposed.