Human gut is colonized by a vast number of microbes known as gut microbiota. The microbiota plays a significant role in the maintenance of health and well-being. A dysbiosis in the microbiota has been associated with the altered metabolism and health disorders. Next-generation sequencing (NGS) aided in taxonomic and functional profiling of the gut microbiome. It has unveiled its richness and diversity. However, little is known about the regulation of microbes in the gut ecosystem, and the underlying interactions with the host. In this chapter, we review recent progress in high-throughput (HT) meta-omics technologies and integrative approaches, with special focus on the utilization of metabolic modeling applied in human along the diet-gut-host axis. We also discuss, how meta-omics and microbiome abundances can be integrated to develop condition-specific gut microbiota models on a genome-scale.