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

Eleonora Scorletti, Paul R. Afolabi, Elizabeth A. Miles, Debbie E. Smith, Amal Almehmadi, Albandri Alshathry, Caroline E. Childs, Stefania Del Fabbro, Josh Bilson, Helen E. Moyses, Geraldine F. Clough, Jaswinder K. Sethi, Janisha Patel, Mark Wright, David J. Breen, Charles Peebles, Angela Darekar, Richard Aspinall, Andrew J. Fowell, Joanna K. DowmanValerio Nobili, Giovanni Targher, Nathalie M. Delzenne, Laure B. Bindels, Philip C. Calder, Christopher D. Byrne

Research output: Contribution to journalArticlepeer-review


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)

Original languageEnglish
Pages (from-to)1597-1610.e7
Issue number6
Publication statusPublished - May 2020


  • Cardiovascular Disease
  • INSYTE Study
  • Nutrition
  • Type 2 Diabetes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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