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Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism's ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections. Author summary: Klebsiella pneumoniae (K. pneumoniae) is a leading cause of nosocomial infections but is considered a silent gut colonizer. A molecular understanding of how K. pneumoniae colonizes the GI tract and overcomes host- and resident gut microbiota-mediated colonization resistance requires further investigation. A direct mechanism of colonization resistance is through competition for the same nutrient resources. K. pneumoniae can sidestep nutrient competition by metabolizing ethanolamine as an alternative nutrient source, thus overcoming microbiota-mediated colonization resistance. The unique ethanolamine utilization loci of K. pneumoniae are both required for robust gut colonization and are conserved among K. pneumoniae, suggesting that ethanolamine metabolism is an important mediator of gut colonization. [ABSTRACT FROM AUTHOR]