Antibiotic-Associated Diarrhea and the Role of Microorganisms in the Gut
Status:
Unknown status
Trial end date:
2021-03-01
Target enrollment:
Participant gender:
Summary
Amoxicillin-clavulanate is an antibiotic commonly prescribed to treat a myriad of
community-acquired infections. One of the most common adverse effects of
amoxicillin-clavulanate is antibiotic-associated diarrhea (AAD). Studies have shown that
administration of antibiotics can cause disruption and changes in the diversity of
microorganisms within the gut (gut microbiome), with overgrowth of "harmful" bacteria as a
possible driver for AAD. How antibiotics specifically affect the gut microbiome to cause AAD
in humans, however, remains unknown. The overall goal of the study is to characterize the
changes in the gut microbiome over time, in subjects who develop AAD after antibiotic
ingestion, and to further demonstrate that resolution of AAD is due to return of "friendly,
anti-diarrhea bacteria". The study investigators will also measure the proteins produced by
the gut bacteria, as a potential tool to help predict which individuals are at risk of AAD.
The investigators plan to recruit 30 healthy adult volunteers who will receive 3 days of oral
amoxicillin-clavulanate, a very commonly prescribed antibiotic. Stool and blood samples will
be collected throughout the study up to 28 days after antibiotic administration. The study
investigators will measure and compare the changes in the gut microbiome and metabolic
responses in order to identify the relationship between these changes and the onset of AAD.
The results from this study will not only yield important scientific knowledge about the
pathogenesis of AAD, but will also provide new leads to understand the interplay between the
gut microbiome, immune-metabolism and AAD. These findings also have the potential to identify
clinically important biomarkers to allow pre-identification of individuals at risk of AAD. If
successful, this study could pave the way for personalized medicine for management of
bacterial infections. This will help to prevent premature stoppage of antibiotic therapy due
to diarrhea side effects, and reduce the risk of bacterial resistance from suboptimal
treatment.