Metformin-induced changes of the gut microbiota in healthy young men: results of a non-blinded, one-armed intervention study

• DOI: 10.1007/s00125-019-4848-7
• Publication Date: 2019-03-23T16:03:31Z
• Authors: Thomas Bryrup; Cæcilie W. Thomsen; Timo Kern; Kristine H. Allin; Ivan Brandslund; Niklas R. Jørgensen; Henrik Vestergaard; Torben Hansen; Tue H. Hansen; Oluf Pedersen; Trine Nielsen
• Keywords: Crossover study

Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared non-diabetic individuals. However, these alterations may be confounded by medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men primary aim investigating metformin-induced compositional changes state. A secondary was to examine whether pre-treatment related gastrointestinal adverse effects during metformin treatment. Twenty-seven young Danish were included 18-week one-armed crossover consisting pre-intervention period, intervention period post-intervention each lasting 6 weeks. Inclusion criteria age 18–35 years, BMI between 18.5 kg/m2 27.5 kg/m2, HbA1c < 39 mmol/mol (5.7%) plasma creatinine within normal range. No prescribed including antibiotics, for months prior recruitment allowed no previous surgery, discounting appendectomy or chronic illness requiring medical During participants given up 1 g twice daily. Participants examined five times fasting state blood sampling recording symptoms. Examinations took place at Frederiksberg Hospital, Denmark before after halfway through immediately end wash-out period. Faecal samples collected nine evenly distributed time points, DNA extracted subjected 16S rRNA gene amplicon sequencing order evaluate composition. Subjective symptoms reported visit. Data from who completed visit (n=23) are analyses. For outcome relative abundance 11 genera significantly changed but returned baseline levels treatment cessation. In line reports, we observed reduced Intestinibacter spp. Clostridium spp., as well increased Escherichia/Shigella Bilophila wadsworthia. The 12 predicted self-reported effects. Intake normoglycaemic men. induced extend validate reports individuals diabetes. Secondary analyses suggest that determinant development following intake. These results require further investigation replication larger prospective studies. Clinicaltrialsregister.eu 2015-000199-86 ClinicalTrials.gov NCT02546050 This project funded Diabetes Association Novo Nordisk Foundation