Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

Casey M. Theriot, Mark J. Koenigsknecht, Paul E. Carlson, Gabrielle E. Hatton, Adam M. Nelson, Bo Li, Gary B. Huffnagle, Jun Z. Li, Vincent B. Young

Research output: Contribution to journalArticle

314 Citations (Scopus)

Abstract

Antibiotics can have significant and long-lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including the primary bile acid taurocholate for germination, and carbon sources such as mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favours C. difficile germination and growth.

Original languageEnglish (US)
Article number3114
JournalNature Communications
Volume5
DOIs
StatePublished - Jan 20 2014

Fingerprint

Clostridium
Clostridium Infections
Metabolome
Clostridium difficile
antibiotics
infectious diseases
mice
Bile Acids and Salts
Anti-Bacterial Agents
germination
magnetic permeability
shift
Germination
acids
Cholestanols
mannitol
Raffinose
Sugar Alcohols
Taurocholic Acid
pathogens

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. / Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun Z.; Young, Vincent B.

In: Nature Communications, Vol. 5, 3114, 20.01.2014.

Research output: Contribution to journalArticle

Theriot, CM, Koenigsknecht, MJ, Carlson, PE, Hatton, GE, Nelson, AM, Li, B, Huffnagle, GB, Li, JZ & Young, VB 2014, 'Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection', Nature Communications, vol. 5, 3114. https://doi.org/10.1038/ncomms4114
Theriot, Casey M. ; Koenigsknecht, Mark J. ; Carlson, Paul E. ; Hatton, Gabrielle E. ; Nelson, Adam M. ; Li, Bo ; Huffnagle, Gary B. ; Li, Jun Z. ; Young, Vincent B. / Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. In: Nature Communications. 2014 ; Vol. 5.
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