Organisms rarely live as isolated species and usually show symbiosis in nature. As natural selection is not simple in symbiosis, the establishment and development of symbiosis is still unclear. Insight can be gained by not only retracing the history of well-developed natural symbiotic relationships, but also by observing the development of nascent symbiosis. By using synthetic symbiosis composed of two previously noninteracting populations, we can observe the establishment and its development. We have recently simulated the establishment of nascent symbiosis using two genetically engineered auxotrophic strains of Escherichia coli. One strain, 10 h after mixing with the partner strain, began to oversupply metabolites essential for the partner's growth, eventually leading to continual growth of both strains. Transcriptome analysis revealed that the oversupply was accompanied by global metabolic changes. This study demonstrated that an organism has the potential to adapt to the first encounter with another organism to establish symbiosis.