Our understanding of the interactions between microbial communities and their niche in the host gut has improved owing to recent advances in environmental microbial genomics. Integration of metagenomic and metataxonomic sequencing data with other omics data to study the gut microbiome has become increasingly common, but downstream analysis after data integration and interpretation of complex omics data remain challenging. Here, we review studies that have explored the gut microbiome signature using omics approaches, including metagenomics, metataxonomics, metatranscriptomics, and metabolomics. We further discuss recent analytics programs to analyze and integrate multi-omics datasets and further utilization of omics data with other advanced techniques, such as adaptive immune receptor repertoire sequencing, microbial culturomics, and machine learning, to evaluate important microbiome characteristics in the gut.