Plain language summary
The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise in parallel with obesity and insulin resistance. Increasing evidence suggests that the gut microbiome may play a role in the pathogenesis of NAFLD, and that prebiotics supplementation is favourably associated with many risk factors common among NAFLD patients. The aim of this study is to provide a protocol for evaluating the efficacy of prebiotic supplementation on hepatic injury and liver fat, the gut microbiota, inflammation, glucose tolerance and satiety in patients with NAFLD. A total of 60 participants will be randomised to a prebiotic supplemented group or isocaloric placebo group for 24 weeks, and all participants will receive dietary counselling to achieve a 10% weight loss. This study protocol highlights the importance of a well-designed trial to improve the available therapies for patients with NAFLD. If this prebiotic intervention is beneficial, the gut microbiota-liver axis may provide novel, inexpensive therapeutic targets for managing NAFLD.
Abstract
BACKGROUND Evidence for the role of the gut microbiome in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is emerging. Strategies to manipulate the gut microbiota towards a healthier community structure are actively being investigated. Based on their ability to favorably modulate the gut microbiota, prebiotics may provide an inexpensive yet effective dietary treatment for NAFLD. Additionally, prebiotics have established benefits for glucose control and potentially weight control, both advantageous in managing fatty liver disease. Our objective is to evaluate the effects of prebiotic supplementation, adjunct to those achieved with diet-induced weight loss, on heptic injury and liver fat, the gut microbiota, inflammation, glucose tolerance, and satiety in patients with NAFLD. METHODS/DESIGN In a double blind, placebo controlled, parallel group study, adults (BMI ā„25) with confirmed NAFLD will be randomized to either a 16 g/d prebiotic supplemented group or isocaloric placebo group for 24 weeks (nā=ā30/group). All participants will receive individualized dietary counseling sessions with a registered dietitian to achieve 10 % weight loss. Primary outcome measures include change in hepatic injury (fibrosis and inflammation) and liver fat. Secondary outcomes include change in body composition, appetite and dietary adherence, glycemic and insulinemic responses and inflammatory cytokines. Mechanisms related to prebiotic-induced changes in gut microbiota (shot-gun sequencing) and their metabolic by-products (volatile organic compounds) and de novo lipogenesis (using deuterium incorporation) will also be investigated. DISCUSSION There are currently no medications or surgical procedures approved for the treatment of NAFLD and weight loss via lifestyle modification remains the cornerstone of current care recommendations. Given that prebiotics target multiple metabolic impairments associated with NAFLD, investigating their ability to modulate the gut microbiota and hepatic health in patients with NAFLD is warranted. TRIAL REGISTRATION ClinicalTrials.gov (NCT02568605) Registered 30 September 2015.
Methodological quality
Allocation concealment
:
Not applicable
