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Wang K. et al. introduced the concept of Microbial-Host isozymes (MHIs) and highlighted their role in mediating microbiota–host interactions. They identified bacterial-derived DPP4 as an isoenzyme affecting glucose tolerance and showed that host DPP4 inhibitors may not effectively target bacterial DPP4. They developed an MHI screen system, identifying 71 MHIs in healthy gut microbiota. Among them, DPP4 isozymes degrade GLP-1, explaining variable responses to sitagliptin. This breakthrough opens new avenues for metabolic disorder treatment. However, the complex nature of gut symbiotic bacteria requires further research to understand MHI mechanisms, regulatory roles, and interactions with the host. Precise interventions in gut microbiota offer personalized approaches to metabolic diseases.

Microbial-host-isozyme: unveiling a new era in microbiome–host interaction