Antibiotics Pave Way for C. Diff Infections - "Antibiotic induced alterations of the gut microbiota alter secondary bile acid production and allow for C. difficile spore germination and outgrowth in the large intestine”
Published: Jan. 6, 2016 in mSphere

Abstract:
It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to C. difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tract and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acids) environments, and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin and vancomycin) and was accompanied by a significant loss of secondary bile acids (DCA, LCA, UDCA, HDCA, and ?MCA). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth was supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and antibiotic related changes are organ-specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes.

Learn more: https://news.ncsu.edu/2016/01/theriot-cdiff/

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