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

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

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. (ClinicalTrials.gov, Number: NCT01680640).

Adult, Bifidobacterium animalis, Biomarkers/analysis, Biopsy, Double-Blind Method, Dysbiosis/complications, Elasticity Imaging Techniques, Feces/microbiology, Female, Gastrointestinal Microbiome/drug effects, Humans, Lipids/analysis, Liver/chemistry, Liver Cirrhosis/prevention & control, Magnetic Resonance Spectroscopy, Male, Middle Aged, Non-alcoholic Fatty Liver Disease/diet therapy, Oligosaccharides/administration & dosage, Proof of Concept Study, Synbiotics/administration & dosage, United Kingdom
0016-5085
1597-1610.e7
Scorletti, Eleonora
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Afolabi, Paul R
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Miles, Elizabeth A
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Smith, Debbie E
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Almehmadi, Amal
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Alshathry, Albandri
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Childs, Caroline E
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Del Fabbro, Stefania
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Bilson, Josh
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Moyses, Helen E
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Clough, Geraldine F
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Sethi, Jaswinder K
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Patel, Janisha
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Wright, Mark
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Breen, David J
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Peebles, Charles
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Darekar, Angela
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Aspinall, Richard
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Fowell, Andrew J
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Dowman, Joanna K
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Nobili, Valerio
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Targher, Giovanni
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Delzenne, Nathalie M
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Bindels, Laure B
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Calder, Philip C
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Byrne, Christopher D
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Scorletti, Eleonora
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Afolabi, Paul R
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Miles, Elizabeth A
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Smith, Debbie E
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Almehmadi, Amal
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Alshathry, Albandri
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Childs, Caroline E
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Del Fabbro, Stefania
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Bilson, Josh
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Moyses, Helen E
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Clough, Geraldine F
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Sethi, Jaswinder K
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Patel, Janisha
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Wright, Mark
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Breen, David J
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Peebles, Charles
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Darekar, Angela
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Aspinall, Richard
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Fowell, Andrew J
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Dowman, Joanna K
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Nobili, Valerio
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Targher, Giovanni
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Delzenne, Nathalie M
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Bindels, Laure B
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Calder, Philip C
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Byrne, Christopher D
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Scorletti, Eleonora, Afolabi, Paul R, Miles, Elizabeth A, Smith, Debbie E, Almehmadi, Amal, Alshathry, Albandri, Childs, Caroline E, Del Fabbro, Stefania, Bilson, Josh, Moyses, Helen E, Clough, Geraldine F, Sethi, Jaswinder K, Patel, Janisha, Wright, Mark, Breen, David J, Peebles, Charles, Darekar, Angela, Aspinall, Richard, Fowell, Andrew J, Dowman, Joanna K, Nobili, Valerio, Targher, Giovanni, Delzenne, Nathalie M, Bindels, Laure B, Calder, Philip C and Byrne, Christopher D (2020) Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology, 158 (6), 1597-1610.e7. (doi:10.1053/j.gastro.2020.01.031).

Record type: Article

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 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. (ClinicalTrials.gov, Number: NCT01680640).

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Accepted/In Press date: 11 January 2020
e-pub ahead of print date: 25 January 2020
Published date: May 2020
Keywords: Adult, Bifidobacterium animalis, Biomarkers/analysis, Biopsy, Double-Blind Method, Dysbiosis/complications, Elasticity Imaging Techniques, Feces/microbiology, Female, Gastrointestinal Microbiome/drug effects, Humans, Lipids/analysis, Liver/chemistry, Liver Cirrhosis/prevention & control, Magnetic Resonance Spectroscopy, Male, Middle Aged, Non-alcoholic Fatty Liver Disease/diet therapy, Oligosaccharides/administration & dosage, Proof of Concept Study, Synbiotics/administration & dosage, United Kingdom

Identifiers

Local EPrints ID: 437223
URI: http://eprints.soton.ac.uk/id/eprint/437223
ISSN: 0016-5085
PURE UUID: 51c9616b-03af-4227-90dc-5d884d05b32c
ORCID for Elizabeth A Miles: ORCID iD orcid.org/0000-0002-8643-0655
ORCID for Caroline E Childs: ORCID iD orcid.org/0000-0001-6832-224X
ORCID for Geraldine F Clough: ORCID iD orcid.org/0000-0002-6226-8964
ORCID for Jaswinder K Sethi: ORCID iD orcid.org/0000-0003-4157-0475
ORCID for Philip C Calder: ORCID iD orcid.org/0000-0002-6038-710X
ORCID for Christopher D Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 22 Jan 2020 17:32
Last modified: 17 Sep 2021 04:01

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Contributors

Author: Eleonora Scorletti
Author: Paul R Afolabi
Author: Debbie E Smith
Author: Amal Almehmadi
Author: Albandri Alshathry
Author: Stefania Del Fabbro
Author: Josh Bilson
Author: Helen E Moyses
Author: Janisha Patel
Author: Mark Wright
Author: David J Breen
Author: Charles Peebles
Author: Angela Darekar
Author: Richard Aspinall
Author: Andrew J Fowell
Author: Joanna K Dowman
Author: Valerio Nobili
Author: Giovanni Targher
Author: Nathalie M Delzenne
Author: Laure B Bindels
Author: Philip C Calder ORCID iD

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