Nanopore Sequencing Expands Individualized Structural Variations in Gut Metagenome

In-depth profiling of genetic variations in the gut microbiome is highly desired for understanding its functionality and impacts on host health and disease. Here, by harnessing the long read advantage provided by Oxford Nanopore Technology (ONT), we have characterized fine-scale genetic variations of structural variations (SVs) in hundreds of gut microbiomes from healthy humans. ONT long reads dramatically improved the quality of metagenomic assemblies, enabled reliable detection of a large, expanded set of structural variations (SVs) types (notably including large insertions and inversions). We found SVs are highly distinct between individuals and stable within an individual, representing gut microbiome fingerprints that shape strain-level differentiations in function within species, complicating the associations to metabolites and host phenotypes such as blood glucose. In summary, our study strongly emphasizes that incorporating ONT reads into metagenomic analyses expands the detection scope of genetic variations, enables profiling strain-level and temporal variations in gut microbiome, and their intricate correlations with metabolome.