Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth

Cell Host Microbe. 2018 Jan 10;23(1):54-64.e6. doi: 10.1016/j.chom.2017.11.006. Epub 2017 Dec 21.


During Salmonella-induced gastroenteritis, mucosal inflammation creates a niche that favors the expansion of the pathogen population over the microbiota. Here, we show that Salmonella Typhimurium infection was accompanied by dysbiosis, decreased butyrate levels, and substantially elevated lactate levels in the gut lumen. Administration of a lactate dehydrogenase inhibitor blunted lactate production in germ-free mice, suggesting that lactate was predominantly of host origin. Depletion of butyrate-producing Clostridia, either through oral antibiotic treatment or as part of the pathogen-induced dysbiosis, triggered a switch in host cells from oxidative metabolism to lactate fermentation, increasing both lactate levels and Salmonella lactate utilization. Administration of tributyrin or a PPARγ agonist diminished host lactate production and abrogated the fitness advantage conferred on Salmonella by lactate utilization. We conclude that alterations of the gut microbiota, specifically a depletion of Clostridia, reprogram host metabolism to perform lactate fermentation, thus supporting Salmonella infection.

Keywords: Salmonella; gut microbiota; host metabolism during infection; host-microbe interaction; microbial metabolism.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Butyric Acid / metabolism
  • Clostridium / growth & development*
  • Dysbiosis / microbiology*
  • Female
  • Fermentation
  • Gastroenteritis / microbiology*
  • Gastroenteritis / pathology
  • Gastrointestinal Microbiome / drug effects*
  • Intestinal Mucosa / microbiology*
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • Lactic Acid / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / agonists
  • Salmonella Infections / pathology
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / metabolism*
  • Triglycerides / pharmacology


  • Anti-Bacterial Agents
  • PPAR gamma
  • Triglycerides
  • Butyric Acid
  • Lactic Acid
  • L-Lactate Dehydrogenase
  • tributyrin