Precision microbiome medicine and therapeutics: the enabling role of <i>in vitro</i> gut models

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.