Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease

Not Applicable

Completed

Interventions: Dietary Supplement: Prebiotic fibre
Dietary Supplement: Placebo
Behavioral: Weight Loss

Brief Summary: Non-alcoholic fatty liver disease (NAFLD) is a condition where accumulation of fat in the liver leads to metabolic dysfunction. Currently there are no approved treatments for NAFLD. Part of the metabolic dysfunction may arise through changes in the gut microbiota. Prebiotic fibres have beneficial effects on glucose tolerance, body weight, and gut microbiota; therefore they may have potential as part of a dietary strategy for NAFLD treatment.

Detailed Description: The main objective of this study is to assess the effect of prebiotic fibre supplementation, in conjunction with diet-induced weight loss, on reduction in liver fat and injury.

Primary Objective - determine the change in hepatic injury (fibrosis and inflammation) and hepatic fat (percent fat) over 6 months in NAFLD patients treated with prebiotic or placebo during weight loss.

Secondary Objectives - determine the changes in appetite, body composition, glycemic and insulinemic responses, quality of life with prebiotic or placebo during weight loss, and examine mechanisms related to prebiotic-induced changes in gut microbiota and lipogenesis.

Recruitment & Eligibility

Inclusion Criteria

Adult subjects diagnosed with NAFLD on the basis of abnormal liver enzymes (ALT>1.5x upper limit of normal) and ultrasonography
Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
Aspartate aminotransferase and alanine aminotransferase ≤10x upper limit of normal
Patients with type 2 diabetes treated with diet and exercise alone or metformin

Exclusion Criteria

Cirrhosis of the liver (FibroScan >17.5 kilopascal or FibroTest >0.8) or clinical features of cirrhosis.
Alcohol consumption >20g/day (2 standard drinks) in women or > 30g/d (3 drinks) in men
Alternate (e.g. TPN) or concomitant etiology for abnormal liver enzymes.
History of decompensated liver disease including ascites, encephalopathy or variceal bleeding
Concomitant use of any weight loss medication, previous bariatric or other intestinal surgery
Presence of active infection, pregnancy or lactation
Regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment
Antibiotic use within 3 months prior to enrollment
Weight loss >3 kg within preceding 3 months to enrollment
Uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections
Use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, Glucagon-like peptide-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid)
Patients with type 2 diabetes where HbA1c is >9%

Arm && Interventions

Group	Intervention	Description
Prebiotic Fibre	Prebiotic fibre	The intervention group will receive two 8g packets/day of prebiotic fibre to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
Placebo	Placebo	The control group will receive two 3g packets/day of maltodextrin to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
Weight Loss	Weight Loss	All participants will be supported through Registered Dietitian visits to achieve approximately 10% weight loss.
Placebo	Weight Loss	The control group will receive two 3g packets/day of maltodextrin to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
Prebiotic Fibre	Weight Loss	The intervention group will receive two 8g packets/day of prebiotic fibre to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.

Primary Outcome Measures

Name	Time	Method
Change in Liver Fat	24 weeks	Assessed via MRI
Change in Liver Fibrosis	24 weeks	Assessed via FibroScan (transient elastography)
Change in Liver Injury	24 weeks	Assessed via Fibrotest Score (composite score from serum biochemical markers: alfa2-macroglobulin, apolipoproteinA1, total bilirubin, haptoglobin, gamma glutamyl transpeptidase, alanine aminotransferase)

Secondary Outcome Measures

Name	Time	Method
Change in Satiety Hormones	24 weeks	Assessed in serum as pg/ml (Ghrelin, Glucagon-like peptide-1, Glucose-dependent insulinotropic polypeptide, leptin and Peptide tyrosine tyrosine)
Change in Glucose Tolerance	24 weeks	Assessed via an oral glucose tolerance test
Dietary Adherence	24 weeks	Assessed via adherence to prescribed versus measured energy intake assessed by food records
Change in Subjective Appetite	24 weeks	Assessed via Subjective appetite ratings on a visual analogue scale
Change in Quality of Life	24 weeks	Assessed via the Short Form-36v2 Health Survey questionnaire
Change in Glycemic Control	24 weeks	Assessed via HbA1c
Change in Body Composition	24 weeks	Assessed via dual x-ray absorptiometry
Examine mechanisms related to prebiotic-induced changes in gut microbiota, their metabolic byproducts, and de novo lipogenesis	24 weeks	Via investigating gut microbiota shot-gun sequencing and measurement of volatile organic compounds and de novo lipogenesis using deuterium incorporation