Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics
Condition: Antibiotic-associated Diarrhea
MeSH terms: Diarrhea
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The focus of the study is to better understand the mechanisms causing antibiotic-associated
      diarrhea (AAD) and how probiotics may prevent some of the iatrogenic effects of antibiotic
      medications. One of the most common indications for probiotics is for prevention of
      antibiotic-associated diarrhea. Clinically, different probiotic strains have demonstrated the
      ability to prevent AAD; however, the mechanism of action behind this effect has not been
      elucidated. Data from several studies suggest that antibiotic-induced disruption of commensal
      bacteria in the colon results in a significant (up to 50%) reduction in short chain fatty
      acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting
      in AAD. Probiotics have been shown to ameliorate a variety of gastrointestinal disease states
      and thus, the study investigators hypothesize that administration of a probiotic yogurt will
      protect against the development of AAD.
    

Detailed description: 
      Probiotics are live microorganisms that, when administered in adequate amounts, confer a
      health benefit on the host. One of the most common indications for probiotic treatment is the
      prevention of antibiotic-associated diarrhea (AAD). Unfortunately, the efficacy of many
      probiotic products used for AAD is not supported by rigorous independent research, and
      non-evidence-based clinical usage is common. Data from several studies are consistent with
      the notion that antibiotic-induced disruption of commensal bacteria in the colon results in a
      significant reduction of short chain fatty acid (SCFA) production and a concomitant reduction
      in Na-dependent fluid absorption resulting in AAD. The probiotic strain being studied,
      Bifidobacterium animalis subsp. lactis BB-12 (BB-12), has been shown to ameliorate a variety
      of gastrointestinal disease states and is known to produce acetate at concentrations up to 50
      mM in vitro. Thus, the investigators hypothesize that administration of BB-12 at the same
      time as antibiotic consumption will protect against the development of AAD through its
      ability to generate acetate directly, and also increase other SCFAs through cross-feeding of
      certain bacteria in the Firmicutes phylum such Clostridium, Eubacterium and Roseburia, which
      use acetate to produce butyrate.

      The primary aim of the R61 phase (N=60) is to determine the ability of BB-12 to impact
      antibiotic-induced reduction in SCFA as reflected by the levels of acetate, the most abundant
      primary colonic SCFA. The primary hypothesis is that antibiotics will result in a reduction
      in fecal SCFA, but BB-12 supplementation will protect against antibiotic-induced SCFA
      reduction and/or be associated with a more rapid return to baseline SCFA levels as compared
      to controls. Antibiotics also result in a decrease in total microbial counts and diversity in
      the gut microbiota, disrupting the homeostasis of the gut ecosystem and allowing colonization
      by pathogens. The secondary aim will be to determine the ability of BB-12 to impact
      antibiotic-induced disruption of the gut microbiota with 16S (16 Svedberg) ribosomal
      ribonucleic acid (rRNA) profiling. The secondary hypothesis is that antibiotics will result
      in a decrease in the overall number and diversity of bacterial species present in the fecal
      microbiota, and further BB-12 supplementation will protect against antibiotic-induced shifts
      in the microbiota and/or will be associated with a more rapid return to a baseline microbiota
      composition as compared to controls. The long-term goal is to determine the impact of BB-12
      on a variety of gastrointestinal disease states and ages, through high-level independent
      research. This mechanism elucidation is important for directing future translational and
      effectiveness research.
    

Intervention name(s): Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; BB-12; Control
Intervention type(s): Drug; Biological; Other
Intervention description(s): Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt; Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)
Other intervention name(s): Augmentin
Intervention MeSH terms: Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other