Throughout thousands of years of evolution, cells have developed various strategies to adapt to short-term or long-term environment fluctuations. However, cell resilience only exists in a certain range. Scientists take advantage of this feature to develop novel treatments for human diseases by regulating environmental factors. To better understand how a change in nutrient level in the environment can influence the cell, the carbon source in the culture media was shifted from a favorable one (mannitol or mannose) to an unfavorable one (acetate) during E. coli growth. The cell growth was monitored, which demonstrated a macroscopic picture of the influence of carbon source shift on E. coli. The cell metabolome before and after the carbon source shift was also investigated. From the untargeted metabolomics analysis, metabolites and metabolic pathways that might be involved in E. coli’s response to carbon source shift were identified. The metabolites and metabolic pathways can indicate specific cell vulnerability caused by lack of nutrients. Future studies can be done with more combinations of pre-shift and post-shift carbon sources and more types of omics studies. What is more, in addition to E. coli, similar nutrient transition studies can be done on cancer cells or diseased neural cells. Once a generalized conclusion is obtained, modulation of nutrient levels in the environment can be put into practical applications.