Bacteriophages in gut metagenomes: from analysis to application

Abstract Bacteriophages constitute a major component of the human gut virome, playing very important roles in shaping of the structure and function of the gut microbiota. Moreover, bacteriophages interact with the human immune system, thereby influencing various disease processes. Recent advancements in metagenomic sequencing and computational analysis have substantially expanded our understanding of gut phage diversity and the scale of the so-called ‘viral dark matter’. In this review, we summarize current bioinformatic approaches for identifying and annotating bacteriophage sequences in metagenomic data, discuss key challenges in taxonomic classification and host prediction of phages, as well as the limitations associated with the assembly and analysis of viral metagenome-assembled genomes (vMAGs). We also analyze the therapeutic potential of bacteriophages, including their application in cancer immunotherapy, inflammatory diseases, and liver diseases, and their promise as diagnostic and prognostic biomarkers.