Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04414722 |
| Other study ID # |
2020-2431 |
| Secondary ID |
R33AT009622 |
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2021 |
| Est. completion date |
May 1, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
Georgetown University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 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, and
assess temporal intervals of probiotic administration. 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. We hypothesize that concurrent
administration of the probiotic and antibiotic is not necessary for the probiotic impact on
SCFA.
The secondary aim will be to determine the ability of BB-12 to impact antibiotic-induced
disruption of the gut microbiota with 16S ribosomal ribonucleic acid (rRNA) profiling, and
assess temporal intervals of probiotic administration. 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. We hypothesize
that concurrent administration of the probiotic and antibiotic is not necessary for the
probiotic effect on the composition of the gut microbiota.
The tertiary aim is to longitudinally characterize the gut microbiota with high-throughput
metatranscriptomics in order to generate complementary information on the impact of
antibiotics plus and minus BB-12 on overall microbiome function. We hypothesize that acetate
produced by BB-12 in situ will cross-feed butyrate producers in the Firmicutes phylum
resulting in an up-regulation of butyrate biosynthetic pathways.
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.
