Effect of Antibiotics on Gut Microbiome and Plasma Metabolome

Study Overview
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Brief Summary
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In recent years it has been observed that the gut microbiome can produce metabolites into systemic circulation and thus have important health effects even outside the gastrointestinal system. These metabolites may play a role in the pathogenesis of common public health problems such as diabetes, obesity and cardiovascular disorders. Modern techniques of mass spectrometry-based metabolomics from peripheral blood and gut metagenome sequencing now enable detailed examination of these processes. Using samples from the FINRISK 2002 cohort, collected by the National Institute for Health and Welfare, we are currently determining the gut microbiome and plasma metabolome from > 7000 participants with 15 years of follow-up for various health outcomes. This is one of the largest materials of its kind world-wide. The design does not, however, allow us to draw causal conclusions on the roles of gut bacteria in the composition of plasma metabolome. To enable conclusions which go beyond statistical associations, we now propose an extension to the FINRISK 2002 study, where we alter the gut bacteriome with a short course of antibiotics and then examine whether a change in plasma metabolomics profile will follow. At the same time the trial will give important novel information about the effects of commonly used antibiotics on gut bacteriome and on general health.

Official Title
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Effect of Antibiotics on Gut Microbiome and Plasma Metabolome

Conditions
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Microbial Colonization

Intervention / Treatment
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* Drug: Amoxicillin
* Drug: Azithromycin
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior participation in the FINRISK 2002 survey and current residence in Helsinki metropolitan area. Age range 40-74 years among men and 50-74 years among women. Exclusion Criteria: Known allergy to any antibiotic A course of antibiotic during the past year Acute infection Any major illness (history of myocardial infarction, stroke, diabetes, liver or kidney disease, cancer, psychiatric disease). Uncomplicated hypertension is allowed. Likewise, statin treatment and women's hormone replacement therapy are allowed.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amoxicillin<br> | Drug: Amoxicillin<br>* Amoxicillin (po) 500 mg x 3 per day for 3 days.<br>|
| Active Comparator: Azithromycin<br> | Drug: Azithromycin<br>* Azithromycin (po) 500 mg x 1 on day 1, 250 mg x 1 on day 2, and 250 mg x 1 on day 3.<br>|
| Active Comparator: Vancomycin<br> | Drug: Vancomycin<br>* Vancomycin (po) 125 mg x 4 per day for 3 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiome | Change in gut microbiome from baseline to repeat assessments. | Baseline: 0 days; repeat assessments 2 days and 28 days after end of antibiotics. | 
| Metabolome | Change in circulating metabolome from baseline to repeat assessments. | Baseline: 0 days; repeat assessments 2 days and 28 days after end of antibiotics. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, metabolize