Antibiotic Induced Depletion of Bile Acids Facilitates Growth of C. diff

Casey M. Theriot, Ph.D. Assistant Professor Infectious Disease College of Veterinary Medicine Department of Population Health and Pathobiology North Carolina State University Raleigh, NC 27607

Dr. Casey Theriot

MedicalResearch.com Interview with:
Casey M. Theriot, Ph.D.
Assistant Professor Infectious Disease
College of Veterinary Medicine
Department of Population Health and Pathobiology
North Carolina State University
Raleigh, NC 27607

Medical Research: What is the background for this study? What are the main findings?

Dr. Theriot: This study is an extension of the work we did in 2014 in our Nature Communications paper (Theriot et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection, 2014). We really wanted to know how different antibiotics that varied in their mechanism of action altered the gut microbiota in different ways and also in turn how this altered the bile acids present in the small and large intestine of mice. Primary bile acids are made by the host and are further converted to secondary bile acids by members of the microbiota in the large intestine. We know from previous work that secondary bile acids can inhibit the growth of C. difficile, but no one has looked in depth at the bile acid makeup in the actual gut before in the context of C. difficile. In this study we show that specific antibiotics that significantly alter the large intestinal gut microbiota and deplete all secondary bile acids allow for C. difficile to grow without any inhibition. We also showed that C. difficile spores are always germinating in the small intestine, which means in order to prevent this pathogen from colonizing the gut, we will have to target the growth of the pathogen. Moving forward the focus will be on trying to repopulate the gut with bacteria that are capable of restoring the secondary bile acid pools in order to inhibit C. difficile.

Medical Research: What should clinicians and patients take away from your report?

Dr. Theriot: Antibiotics are very important for treating bacterial infections, but they can have unforeseen consequences. Depending on the antibiotic it can significantly alter your gut microbiota, which in turn will alter the production of small molecules or metabolites that are produced. Some of the small molecules, like secondary bile acids, are important for preventing colonization of enteric pathogens like C. difficile. But, there is also a fine balance here as well. I think this study further drives home that the prudent use of antibiotics is very important.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Theriot: I think future research needs to focus more on targeted bacterial approaches for combating C. difficile. We know that fecal transplants are very effective against C. difficile infections, but we do not yet understand the mechanism behind this. Feces is made up of many different bacteria that have many different functions and trying to break down what a single bacterium is doing in that large community will be hard, but it is important. On the other hand, if we know what products the bacteria are making that are able to prevent C. difficile from growing in the gut, then let’s use this to our advantage. We can now start to identify bacteria that are capable of altering the bile acid pools in the gut, including bacteria that are capable of producing secondary bile acids, in hopes of reengineering the gut so that it is resistant against C. difficile colonization.

Citation:

Casey M. Theriot, Vincent B. Young, Alison A. Bowman. Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine. mSphere, January 2016 DOI:10.1128/mSphere.00045-15

Casey M. Theriot, Ph.D (2016). Antibiotic Induced Depletion of Bile Acids Facilitates Growth of C. diff 

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