Abstract
The human microbiome is increasingly recognized as a fundamental regulator of health and disease, influencing metabolic homeostasis, immune signaling, and host–microbe interactions. Advances in high-throughput sequencing technologies and integrated multi-omics platforms have transformed microbiome research, enabling comprehensive characterization of microbial communities and their functional outputs with clinical
relevance.
Aim: This review aims to critically evaluate recent progress in human microbiome research, with a particular focus on how multi-omics approaches are enhancing mechanistic understanding, refining clinical diagnostics, and enabling microbiome-based therapeutic interventions within a precision-medicine framework.
Methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science to identify peer-reviewed original studies and systematic reviews published between 2020 and March 31, 2025. Studies employing genomics, metagenomics, transcriptomics, proteomics, and metabolomics were analyzed, with emphasis on translational and clinical applicability.
Results: Integrated multi-omics analyses reveal complex interactions between microbial metabolites such as short-chain fatty acids, secondary bile acids, and tryptophan derivatives and host immune and metabolic pathways. Microbiome-derived signatures have demonstrated predictive potential for metabolic and inflammatory disorders, including type 2 diabetes, supporting their role as diagnostic and prognostic biomarkers. Therapeutic developments include targeted modulation of the microbiota through probiotics, prebiotics, postbiotics, and faecal microbiota transplantation, with increasing evidence from clinical studies.
Conclusion: By integrating mechanistic insights, multi-omics diagnostics, and emerging microbiome-based therapies, this review provides an original, clinically oriented synthesis of the field. Although microbiome-guided interventions offer significant promise for personalized medicine, challenges related to methodological standardization, data governance, regulatory oversight, and equitable access must be addressed to facilitate routine clinical implementation.

Key words: Keywords: human microbiome, microbiome diversity, microbiome-based diagnostics, multi-omics, microbiota-targeted therapies