Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics

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.