Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease

Gastroenterology. 2020 May;158(6):1597-1610.e7. doi: 10.1053/j.gastro.2020.01.031. Epub 2020 Jan 25.


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 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies 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, the fecal microbiome were analyzed by 16S ribosomal DNA 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% confidence interval, -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% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis.

Conclusions: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (, Number: NCT01680640).

Keywords: Cardiovascular Disease; INSYTE Study; Nutrition; Type 2 Diabetes.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bifidobacterium animalis
  • Biomarkers / analysis
  • Biopsy
  • Double-Blind Method
  • Dysbiosis / complications
  • Dysbiosis / diet therapy*
  • Elasticity Imaging Techniques
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Lipids / analysis
  • Liver / chemistry
  • Liver / diagnostic imaging
  • Liver / drug effects*
  • Liver / pathology
  • Liver Cirrhosis / prevention & control
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / diet therapy*
  • Non-alcoholic Fatty Liver Disease / microbiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Oligosaccharides / administration & dosage
  • Proof of Concept Study
  • Synbiotics / administration & dosage*
  • United Kingdom


  • Biomarkers
  • Lipids
  • Oligosaccharides

Associated data