Author information
1 Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK; Department of Gastroenterology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: e.scorletti@soton.ac.uk.
2 Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK
3Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
4 National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK.
5 Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
6 Hepatology, Department of Medicine, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
7 Department of Radiology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
8 Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
9 Department of Hepatology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Portsmouth, UK.
10 Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy; Department of Pediatric, University "La Sapienza", Rome, Italy.
11 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
12 Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
13 Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
Abstract
BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease(NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD.
METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8±12.6 y; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subsp. lactis BB-12; n=55) or placebo (n=49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study and fecal microbiomes were analyzed by 16S rDNA sequencing.
RESULTS: Mean baseline and end of study magnetic resonance spectroscopy liver fat percentage values were 32.3%±24.8% and 28.5%±20.1% in the synbiotic group and 31.3%±22% and 25.2%±17.2% in the placebo group. In the unadjusted intention to treat analysis, we found no significant difference in liver fat reduction between groups (β=2.8; 95% CI, -2.2 to 7.8; P=.30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (β=2; 95% CI, 1.5-2.6; P=.03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium, and reductions in Oscillibacter and Alistipes, compared with baseline; these changes were not observed in the placebo group. Changes in composition of fecal microbiota were not associated with liver fat or markers of fibrosis.
CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 y administration of a synbiotic combination (probiotic and prebiotic) altered fecal microbiomes but did not reduce liver fat content or markers of liver fibrosis. clinicaltrials.gov no: NCT01680640.