Eleonora Scorletti1, Paul R Afolabi2, Elizabeth A Miles3, Debbie E Smith4, Amal Almehmadi3, Albandri Alshathry3, Helen E Moyses2, Geraldine F Clough3, Mark Wright5, Janisha Patel5, Laure Bindels6, Nathalie M Delzenne6, Philip C Calder4, Christopher D Byrne4. 1. Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK. Electronic address: e.scorletti@soton.ac.uk. 2. National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK. 3. Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK. 4. Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK; National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton National Health Service (NHS) Foundation Trust, Southampton, UK. 5. Hepatology, University Hospital Southampton NHS Foundation Trust, Southampton, UK. 6. Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
Abstract
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. DESIGN: In a randomised double-blind placebo-controlled trial, 104 participants were randomised to 10-14 months intervention with eithersynbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. METHODS: Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640. Crown
RCT Entities:
BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of fat-related conditions ranging from simple fatty liver, to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. There is growing evidence that NAFLD is a multisystem disease, affecting several extra-hepatic organs and regulatory pathways. Furthermore, since the gut and liver are linked anatomically via the portal vein, disturbances of the gut microbiota (dysbiosis) can affect the liver. OBJECTIVES: In patients with NAFLD, we are testing the effects of a synbiotic which is the combination of a prebiotic (fructooligosaccharides; 4 g/day) and a probiotic (Bifidobacterium animalis subsp. lactis BB-12 at a minimum of 10 billion CFU/day) on a) liver fat percentage, b) NAFLD fibrosis algorithm scores, c) gut microbiota composition. Additionally, there will be several hypothesis-generating secondary outcomes to understand the metaorganismal pathways that influence the development and progression of NAFLD, type 2 diabetes, and cardiovascular risk. DESIGN: In a randomised double-blind placebo-controlled trial, 104 participants were randomised to 10-14 months intervention with either synbiotic (n = 55) or placebo (n = 49). Recruitment was completed in April 2017 and the last study visit will be completed by April 2018. METHODS: Change in gut microbiota composition will be assessed using 16S ribosomal RNA gene sequencing. Change in mean liver fat percentage will be quantified by magnetic resonance spectroscopy (MRS). In addition, change in liver fat severity will be measured using two NAFLD fibrosis algorithm scores. The INSYTE study was approved by the local ethics committee (REC: 12/SC/0614) and is registered at www.clinicaltrials.gov as NCT01680640. Crown
Authors: 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 Dowman; Valerio Nobili; Giovanni Targher; Nathalie M Delzenne; Laure B Bindels; Philip C Calder; Christopher D Byrne Journal: Gastroenterology Date: 2020-01-25 Impact factor: 33.883
Authors: Geraldine F Clough; Andrew J Chipperfield; Marjola Thanaj; Eleonora Scorletti; Philip C Calder; Christopher D Byrne Journal: Front Physiol Date: 2020-06-03 Impact factor: 4.566
Authors: Josh Bilson; Eleonora Scorletti; Laure B Bindels; Paul R Afolabi; Giovanni Targher; Philip C Calder; Jaswinder K Sethi; Christopher D Byrne Journal: Nutr Diabetes Date: 2021-10-18 Impact factor: 5.097
Authors: Oluyemi Komolafe; Elena Buzzetti; Audrey Linden; Lawrence Mj Best; Angela M Madden; Danielle Roberts; Thomas Jg Chase; Dominic Fritche; Suzanne C Freeman; Nicola J Cooper; Alex J Sutton; Elisabeth Jane Milne; Kathy Wright; Chavdar S Pavlov; Brian R Davidson; Emmanuel Tsochatzis; Kurinchi Selvan Gurusamy Journal: Cochrane Database Syst Rev Date: 2021-07-19