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

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.

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%