The human gut is colonized by different types of microorganisms, which are known to play important roles in the human host by maintaining physiological homeostasis. The human host provides a nutrient-rich environment, and the microbiota provides some necessary functions that humans cannot perform. A comprehensive analysis of the human gut microbiome is thus important for revealing the mechanisms of these host–microbe interactions. The development of high-throughput sequencing technology and related computational frameworks enables exploration of the metabolic interactions and their roles in human health and diseases. Herein, we describe the metagenomic methods used in human gut microbiome studies and review the roles of gut microbiota as well as the integrative analyses of metagenomic data with other omics data. Finally, we discuss the application of constraint-based modeling to elucidate the microbe–microbe interaction and host–microbe interaction in the human gut microbiota.