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Enterobacteriaceae are intestinal residents, but generally represent &amp;lt;1% of the adult colonic microbiota. Antibiotic-mediated destruction of the microbiota enables Enterobacteriaceae to expand to high densities in the colon, markedly increasing the risk of bloodstream invasion, sepsis, and death. Here, we demonstrate that an antibiotic-naive microbiota suppresses growth of antibiotic-resistant clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis by acidifying the proximal colon and triggering short chain fatty acid (SCFA)\u2013mediated intracellular acidification. High concentrations of SCFAs and the acidic environment counter the competitive edge that O2 and NO3 respiration confer upon Enterobacteriaceae during expansion. Reestablishment of a microbiota that produces SCFAs enhances clearance of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis from the intestinal lumen and represents a potential therapeutic approach to enhance clearance of antibiotic-resistant pathogens.<\/jats:p>","DOI":"10.1084\/jem.20181639","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T15:09:19Z","timestamp":1545145759000},"page":"84-98","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":265,"title":["Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification"],"prefix":"10.1084","volume":"216","author":[{"given":"Matthew T.","family":"Sorbara","sequence":"first","affiliation":[{"name":"Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 1"},{"name":"Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer 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