The microbial community in the mammalian intestine confers protection from the expansion of pathogenic bacteria. However, the disruption of microbial community composition has been linked to the emergence of infections, and treatment with antibiotics promotes the relapse of gastroenteritis caused by Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). Now, Rivera-Chávez et al. show that treatment with streptomycin reduces the abundance of butyrate-producing Clostridia in the mouse intestinal lumen; the resulting decrease in butyrate availability increases the oxygenation of epithelial cells and promotes the aerobic expansion of S. Typhimurium. Lumenal expansion was shown to be driven by the bacterial cytochrome bd-II oxidase, and could be diminished by increasing the abundance of Clostridia and by restoring hypoxia. Finally, infection with S. Typhimurium in mice that are genetically resistant to S. Typhimurium depleted Clostridia in the absence of antibiotic treatment through virulence factor-induced intestinal inflammation, thus enabling the aerobic growth of the pathogen.