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

By C. Theriot, M. Koenigsknecht, Paul E. Carlson, G. Hatton, Adam M. Nelson, Bo Li, G. Huffnagle, Jun Li, Vincent B. Young. Nature Communications, 2014

935 citations recorded by the source corpus.

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. Antibiotics alter the intestinal microbiota and facilitate colonization of pathogens such as Clostridium difficile. Here, the authors show that antibiotic-induced shifts in the mouse gut microbiome are correlated with changes in levels of certain metabolites that C. difficilecan use for germination and growth.

Subfields: Gastroenterology, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9c0f17a92ce1c28b56d51efd4c257b97168683c9

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In Molecular Biology

1. Nihal Hasan
2. Gautam Dantas
3. J. Durack
4. S. Lynch
5. Hongyi Yang
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Citations in the corpus

• Factors affecting the composition of the gut microbiota, and its modulation (2019, background): “difficile for essential nutrients (Buffie et al., 2015; Theriot et al., 2014), and this could prevent CDI.”
• The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation (2016, background): “In addition to high-throughput analysis of gene content, the use of metatranscriptomics [19], metaproteomics [20], and metametabolomics [21]”
• Mechanisms and consequences of intestinal dysbiosis (2017, background): “difficile, some microbes transform bile acids, thereby reducing the rate of germination of clostridial spores in the gut [236].”
• The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Persistent antibiotic-induced colitis Antibiotic-induced alterations in the gut microbiome and its associated metabolome reduce colonization resistance against the spore-forming, toxin-producing pathogen Clostridium difficile (Theriot et al., 2014), a causative agent of antibiotic-associated colitis”
• Biology and Diseases of Mice (2015, positive): “A recent study in C57BL mice demonstrated that antibiotic-mediated alteration of the gut microbiome favors a global metabolic profile, and therefore increases susceptibility to C. difficile clinical diseases (Theriot et al., 2014) .”