Translational approaches in microbiome research: from functional mechanisms to next-generation therapeutics

Microbiome research has made substantial progress toward clinical translation over the past 2 decades, moving from associative observations toward mechanistic investigation, validation, and therapeutic intervention. This narrative review examines recent advances in the clinical application of microbiome research over the past 5 years, focusing on non-invasive microbiome-derived biomarkers and therapeutic strategies, including personalized probiotics and prebiotics, fecal microbiota transplantation (FMT), and engineered microbial therapeutics, while evaluating the strength of the supporting evidence. Microbiota-based treatments for recurrent Clostridium difficile infection are currently at the forefront of clinical translation, whereas applications in inflammatory, metabolic, neurological, and oncological disorders remain largely investigational. We further examine these translational barriers while highlighting opportunities to integrate microbiome data with systems biology and advanced analytics to improve clinical outcomes and advance precision medicine. By linking mechanistic discoveries with their current level of clinical development, this narrative review critically evaluates the available translational microbiome evidence, identifies key bottlenecks and unresolved knowledge gaps, and outlines priorities for the responsible integration of microbiome-based diagnostics and therapeutics into clinical practice.