Effect of Antibiotics on Gut Microbiome and Plasma Metabolome

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.

Study Overview

• Status: Completed
• Conditions: Microbial Colonization
• Intervention / Treatment: Drug: Amoxicillin; Drug: Azithromycin; Drug: Vancomycin

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00271
    • National Institute for Health and Welfare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Amoxicillin	Drug: Amoxicillin; Amoxicillin (po) 500 mg x 3 per day for 3 days.
ACTIVE_COMPARATOR: Azithromycin	Drug: Azithromycin; Azithromycin (po) 500 mg x 1 on day 1, 250 mg x 1 on day 2, and 250 mg x 1 on day 3.
ACTIVE_COMPARATOR: Vancomycin	Drug: Vancomycin; Vancomycin (po) 125 mg x 4 per day for 3 days.

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Finnish Institute for Health and Welfare
• Collaborators: University of California, San Diego; Brigham and Women's Hospital
• Investigators: Principal Investigator: Markus Perola, MD, PhD, Finnish Institute for Health and Welfare

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2017
• Primary Completion (ACTUAL): December 15, 2017
• Study Completion (ACTUAL): December 15, 2017

Study Registration Dates

• First Submitted: September 4, 2017
• First Submitted That Met QC Criteria: September 4, 2017
• First Posted (ACTUAL): September 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2018
• Last Update Submitted That Met QC Criteria: April 3, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: microbiota; metabolize
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Amoxicillin; Azithromycin
• Other Study ID Numbers: 1341/6.00.00/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No