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Synbiotic alters fecal microbiomes, but not liver fat or fibrosis, in a randomized trial of patients with non-alcoholic fatty liver disease

Synbiotic alters fecal microbiomes, but not liver fat or fibrosis, in a randomized trial of patients with non-alcoholic fatty liver disease
Synbiotic alters fecal microbiomes, but not liver fat or fibrosis, in a randomized trial of patients with non-alcoholic 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 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 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 and fecal microbiomes 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% 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 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiomes but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, no: NCT01680640)
Cardiovascular Disease, INSYTE Study, Nutrition, Type 2 Diabetes
0016-5085
1597-1610.e7
Scorletti, Eleonora
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Afolabi, Paul
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Miles, Elizabeth
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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, Natalie M.
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Bindels, Laure B.
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Calder, Philip C.
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Scorletti, Eleonora
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Afolabi, Paul
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Miles, Elizabeth
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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, Natalie 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, Miles, Elizabeth, 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, Natalie M., Bindels, Laure B., Calder, Philip C. and Byrne, Christopher D. (2020) Synbiotic alters fecal microbiomes, but not liver fat or fibrosis, in a randomized trial of patients with non-alcoholic 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 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 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 and fecal microbiomes 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% 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 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiomes but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, no: 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: Cardiovascular Disease, INSYTE Study, Nutrition, Type 2 Diabetes

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 Paul Afolabi: ORCID iD orcid.org/0000-0002-0553-1578
ORCID for Elizabeth 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 Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 22 Jan 2020 17:32
Last modified: 18 Feb 2021 17:32

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Contributors

Author: Eleonora Scorletti
Author: Paul Afolabi ORCID iD
Author: Elizabeth Miles ORCID iD
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: Natalie M. Delzenne
Author: Laure B. Bindels

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