Precision microbiome medicine and therapeutics: the enabling role of in vitro gut models

Abstract The human gut microbiome exhibits profound interindividual variability, challenging the efficacy of generalized interventions and underscoring the need for precision approaches to microbiome-associated diseases. Such strategies require comprehensive, individualized assessment of microbial ecosystems and their functional responses, an objective that remains difficult to achieve in vivo. In vitro gut models offer a promising alternative, maintaining personalized microbial communities in controlled environments and enabling detailed investigation of microbiome dynamics. Complementary microbe–host co-culture systems incorporating human cells further permit mechanistic interrogation of host responses to microbial stimuli. Together, these integrated platforms offer a translational framework for developing tailored therapeutics. In this Perspective, we examine how in vitro gut models can advance microbiome-based personalized medicine, discuss key determinants of therapeutic variability, and outline the relevance, limitations, and future directions of these systems in designing targeted, more effective interventions.