From microbiome to metabolism: Bridging a two-decade translational gap

The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.