@article{c189931947124acd8f54581dace92712,
title = "Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection",
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.",
author = "Theriot, {Casey M.} and Koenigsknecht, {Mark J.} and Carlson, {Paul E.} and Hatton, {Gabrielle E.} and Nelson, {Adam M.} and Bo Li and Huffnagle, {Gary B.} and Li, {Jun Z.} and Young, {Vincent B.}",
note = "Funding Information: We give credit to Christine Bassis for the image displayed on the Nature Communications website, showing C. difficile-infected mouse colon labelled by fluorescence in situ hybridization. We thank Kathy Wozniak and Charles Koumpouras for assisting with the animal studies of C. difficile. We also thank Sue Foltin for conducting the 454-pyrosequencing run. We thank Charles Evans, Chunhai Ruan and Li Zhang at the Metabolomics Core Services, supported by Grant DK097153 of NIH Common Funds Project to the University of Michigan, for the development and execution of the targeted metabolomic analysis. The untargeted metabolomic analysis was done in collaboration with Edward Karoly at Metabolon Inc. Durham, NC. We thank Dale Gerding and Adam Cheknis for providing C. difficile clinical isolate BI/NAP1/027, strain reference number H290. This work was funded by NIH Grant U19AI090871 (P.E.C., J.L., G.B.H. and V.B.Y.). A.M.N. was funded by training Grant T32 HL007749, M.J.K. by training Grant T32 AI007528 and C.M.T. by training Grants T32 HL007749 and a career development Grant K01 GM109236.",
year = "2014",
month = jan,
day = "20",
doi = "10.1038/ncomms4114",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}