Microbiome-Guided Precision Medicine: Mechanistic Insights, Multi-Omics Integration, and Translational Horizons

The human microbiome is increasingly recognized as a critical modulator of host physiology, offering a dynamic and targetable axis in the landscape of precision medicine. This review critically examines the mechanistic pathways through which the microbiome influences immunity, metabolism, pharmacological response, and gene regulation, with emphasis on disease-specific interactions spanning oncology, immunology, metabolic disorders, and neuropsychiatry. Multi-omics technologies, including metagenomics, metatranscriptomics, metaproteomics, and metabolomics, are explored as integrative tools that generate a systems-level understanding of host–microbe interactions. Computational frameworks for data integration and interpretation are discussed, alongside clinical applications in microbiome-informed diagnostics, patient stratification, and therapeutic interventions such as fecal microbiota transplantation and engineered probiotics. Persistent challenges, ranging from inter-individual variability and data standardization to ethical and regulatory complexities, are evaluated with reference to emerging solutions, including synthetic biology, personalized microbial interventions, and decision-support algorithms. The review underscores the need for collaborative, mechanistically anchored, and longitudinal approaches to fully translate microbiome science into actionable precision health strategies.