SEP 13, 2017 6:00 AM PDT

Next-generation probiotics targeting C. difficile infection

Speaker
  • Instructor, Pathology & Immunology, Baylor College of Medicine
    Biography
      Dr. Spinler is an experienced classical microbiologist with extensive training in bacterial genetics and genomics currently serving as faculty at Baylor College of Medicine in the Texas Children's Microbiome Center. Her expertise in developing mutagenesis systems for investigations of gram-positive bacteria which has contributed to recent successes with genetics of probiotics; particularly in the area of antimicrobial production by Lactobacillus reuteri. Current research efforts combine comparative and functional genomics strategies with animal models and microbiome research to understand how individual probiotic organisms beneficially impact the larger microbiome community of the gastrointestinal tract and how these interactions protect against antibiotic-associated disease. Specifically, her research is aimed at developing adjunct probiotic therapies targeting C. difficile infection. As a probiotic researcher in a hospital-based microbiome center, Dr. Spinler has the benefit of combining her expertise with clinically relevant microbiome studies which has tremendous potential to impact our basic understanding of mechanisms of bacterial resistance and create new translational opportunities combatting antimicrobial resistance.

    Abstract

    Adjunct probiotic therapy has the potential to decrease Clostridium difficile disease incidence and severity. After screening several potential probiotic bacteria for intrinsic resistance to C. difficile antibiotics (vancomycin, metronidazole and fidaxomicin), we determined that L. reuteri strains are ideal adjunct therapy candidates. We evaluated the ability of reuterin - a secondary metabolite produced by specific strains of L. reuteri during fermentation of the prodrug glycerol - to inhibit C. difficile growth in vitro.  We found that levels of reuterin produced by L. reuteri 17938 were more potent than vancomycin in inhibiting C. difficile growth. Using human fecal microbiota bioreactors, we showed that co-delivery of L. reuteri with glycerol is effective against C. difficile colonization of a complex-microbial community, whereas treatment with either glycerol or L. reuteri alone was ineffective.  Co-delivery of L. reuteri and glycerol changed microbial community profiles and associated metabolites consistent with glycerol fermentation and reuterin production.  Ex vivo studies showed that this combination therapy resulted in lower C. difficile burden and toxicity in stool and that this was dependent upon reuterin production. Taken together, prodrug-based adjunct therapy with probiotic L. reuteri is a viable option for preventative treatment of C. difficile infection.  

     


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