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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.
Eleonora Scorletti,Paul R Afolabi,Elizabeth A Miles,Debbie E Smith,Amal Almehmadi,Albandri Alshathry,Caroline E Childs,Stefania Del Fabbro,Josh Beavis,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 Dowman,Valerio Nobili,Giovanni Targher,Nathalie M Delzenne,Laure B Bindels,Philip C Calder,Christopher D Byrne