Human gut microbiome study through metagenomics: Recent advances and challenges for clinical implementation

Metagenomics has decisively advanced the study of the gut microbiome, enabling a better understanding of its importance for human health. Metataxonomics, based on the sequencing of the 16S rRNA gene, provides taxonomic profiles of prokaryotes, while shotgun metagenomics allows a comprehensive characterization of all DNA present in a sample. With adequate sequencing depth, the latter increases taxonomic resolution to the strain level and provides detailed information on the functional potential of the microbiota. However, the lack of standardization in sample collection and processing, sequencing technologies, and data management limits the comparability of results and their implementation in clinical laboratories. This review offers a practical and updated framework on metagenomic methodologies, data analysis, and the application of artificial intelligence tools, highlighting advances and best practices to facilitate the integration of functional microbiome analysis into clinical practice and to overcome current challenges.