The human microbiome can be fully understood and manipulated solely through the use of whole-genome shotgun metagenomic sequencing techniques.

Whole‑genome shotgun metagenomics can tell us which genes and organisms are present, but it does not reveal how those microbes behave, how they interact with the host, or how they respond to environmental changes. Because the technique only captures DNA, it misses RNA transcripts, protein activity, and metabolic fluxes that are essential for understanding function. For example, a shotgun survey might find a gene for a toxin, yet without transcript or protein data we cannot know if the toxin is actually produced or how it affects nearby cells. Therefore, while shotgun sequencing is a powerful first step, it must be combined with transcriptomics, metabolomics, and experimental validation to fully understand and manipulate the microbiome.