# Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics

> **NIH NIH R33** · GEORGETOWN UNIVERSITY · 2022 · $288,211

## Abstract

Abstract
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
suggest antibiotic-induced disruption of commensal colonic bacteria results in a significant reduction in short
chain fatty acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption, ultimately
resulting in AAD. The probiotic strain 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 – the most abundant
primary colonic SCFA – at concentrations of up to 50 mM in vitro. Thus, we hypothesize that the concurrent
administration of BB-12 with antibiotics will protect against the development of AAD by the ability of BB-12 to
both generate acetate directly, and increase other SCFAs through cross-feeding of certain bacteria in the
Firmicutes phylum. For example, Clostridium, Eubacterium and Roseburia use acetate to produce butyrate,
another common SCFA. The primary aim of the R61 phase (N=60) is to determine if BB-12 can mitigate
antibiotic-induced reduction in SCFA concentration, as reflected in fecal acetate levels. We hypothesize that
antibiotics will decrease fecal SCFAs, but BB-12 supplementation will protect against antibiotic-induced SCFA
reduction, and/or be associated with quicker restoration to baseline SCFA levels as compared to control.
Antibiotic administration also lowers total microbial counts and diversity in the gut microbiota, disrupting the
homeostasis of the gut ecosystem and allowing colonization by pathogens. The secondary aim uses 16S rDNA
profiling to determine if BB-12 inhibits antibiotic-induced disruption of the gut microbiota. We hypothesize that
antibiotics will diminish the overall number and diversity of bacterial species present in the fecal microbiota,
and concurrent BB-12 supplementation will minimize antibiotic-induced shifts in the microbiota, and/or will be
associated with shorter recovery to baseline microbiota composition as compared to control. In the R33 phase
(N=108), to further delineate the effects of BB-12 administration on the antibiotic-depleted gut microbiota, we
will evaluate the timing of probiotic administration in four randomly assigned groups: 1) BB-12 yogurt
consumed at the same time as the antibiotic; 2) control yogurt consumed at the same time as the antibiotic; 3)
BB-12 yogurt consumed four hours after the antibiotic; and 4) control yogurt consumed four hours after the
antibiotic. Our long-term goal is to determine the impact of BB-12 on a variety of gastrointestinal disease states
and ages. Elucidation of the mechanism(s) of action will b...

## Key facts

- **NIH application ID:** 10480824
- **Project number:** 5R33AT009622-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** DANIEL J MERENSTEIN
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $288,211
- **Award type:** 5
- **Project period:** 2018-09-11 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480824

## Citation

> US National Institutes of Health, RePORTER application 10480824, Exploratory Pilot Studies to Demonstrate Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics (5R33AT009622-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10480824. Licensed CC0.

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