The aim of the study is to assess the effect of eradication of gut microbiota on 1) glucose metabolism including postprandial plasma responses of the incretin hormones GIP and GLP-1, insulin, C-peptide and glucagon, 2) metabolomic profiles and resting energy expenditure (REE) 3) appetite, satiety, food intake, gastric emptying and gall bladder emptying, 4) levels of markers of bone formation and resorption as well as serotonin, 5) markers of systemic inflammation, and 6) on the (prospective) composition of bacteria in faeces, blood and saliva. Thus, the overall objective is to provide detailed knowledge on the physiological role of gut microbiota combined with bioinformatic analyses of the functional implications of changes in bacteria composition on the level of both species and phylum.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
4 days antibiotic treatment, per oral, once daily: vancomycin 500 mg (Vancomycin "Hospira"), powder for concentrate; gentamycin 40 mg ("Hexamycin®"), solution; meropenem 500 mg (Meropenem "Hospira"), powder for concentrate; The three drugs are dissolved and combined to a cocktail (with approximately 100 ml of apple juice)
Gentofte University Hospital
Hellerup, Denmark
changes in postprandial GLP-1 secretion
plasma level of GLP-1 at baseline and during a 4 hour-meal test
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in postprandial insulin/c-peptide secretion
plasma level of insulin/C-peptide at baseline and during a 4 hour-meal test
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in postprandial glucose levels
plasma level of glucose at baseline and during a 4 hour-meal test
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in postprandial GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin secretion
plasma levels of GLP-2, glucagon, PYY, oxyntomodulin, gastrin, CCK, GIP, leptin, adiponectin and ghrelin at baseline and during a 4 hour-meal test
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in markers of bone formation and resorption
fasting plasma levels of osteocalcin, P1NP, CTX, 1CTP, sklerostin and serotonin
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
gut microbiome composition
faecal bacterial composition determined from microbiological cultures and deep metagenomic next-generation sequencing of bacterial DNA in feces
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
changes in markers of systemic inflammation
plasma levels of high sensitive CRP, LPBP, TNF-alfa, IL-6 and PAI
Time frame: 0, 4, 42 and 180 days after antibiotic eradication of gut bacteria
changes in glycated hemoglobin (HbA1c)
plasma level of glycated hemoblobin
Time frame: 42 days after antibiotic eradication of gut bacteria
changes in body weight
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
changes in basal metabolic rate and respiratory quotient
indirect calorimetry measurements (210 minutes postprandial)
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in gastric emptying
1,5 grams of paracetamol will be added to a standardized meal, plasma paracetamol will be measured at baseline and succeeding 4 hours postprandial
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
changes in gall bladder emptying
ultrasonic determination of gall bladder dimensions at baseline and during a 4 hour-meal test (expressed as gall bladder ejection fraction)
Time frame: 0, 4 and 42 days after antibiotic eradication of gut bacteria
appetite, satiety and food intake
the impact of eradication on alimentary processes and appetite regulation will be measured using questionnaires and food intake measures
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
changes in ketone metabolism
measurement of fasting plasma beta-hydroxybutyrate level
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
changes in bile acid deconjugation
measurement of feces bile acid (conjugated and deconjugated) concentration to study the effect of gut microbiome presence on bile acid deconjugation
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
changes in plasma lipid levels
fasting plasma levels of triglyceride, VLDL, LDL, HDL, total cholesterol, in addition: measurements of free fatty acids during a 4 hour meal 0, 4 and 42 days after eradication (not on day 8 and 180)
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
microbiome in blood, urine and saliva
measurements on bacteria or bacterial components in blood, urine and saliva to study the effects of gut eradication on blood, urine and saliva microbiome
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
adverse effects of the used antibiotics
standardized questionaries regarding gastointestinal function are filled out at each study visit (0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria) to detect possible adverse effects of antibiotics. In addition, subjects are given a calendar and informed to write down any symptom or illness during the study period.
Time frame: up to 180 days after antibiotic eradication of gut bacteria
changes in metabolomic profile
plasma and urine samples for metabolomic analysis
Time frame: 0, 4, 8, 42 and 180 days after antibiotic eradication of gut bacteria
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