Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss although difficult to maintain. Emerging evidence indicates that prebiotics and antibiotics improve NAFLD. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD. Methods: Sixty-two people with NAFLD commenced 4-week VLCD using Optifast meal replacements (600 kcal/day). Sixty were then randomised into a 12-week double-blind, placebo-controlled, parallel three-arm trial: (1) 400 mg metronidazole twice daily in Week 1 then inulin 4 g twice daily OR (2) placebo twice daily in week one then inulin OR (3) placebo-placebo. Main outcomes were ALT and body weight at 12 weeks. Fecal microbiota changes were also evaluated. Results: Mean body mass index (BMI) and ALT reduced after VLCD by 2.4 kg/m2 and 11 U/L, respectively. ALT further decreased after metronidazole-inulin compared to after placebo-placebo (mean ALT change −19.6 vs. −0.2 U/L, respectively; p = 0.026); however, weight loss maintenance did not differ. VLCD treatment decreased the ratio of Firmicutes/Bacteroidetes (p = 0.002). Conclusion: Brief metronidazole followed by inulin supplementation can reduce ALT beyond that achieved after VLCD in patients with NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is defined by the pathological accumulation of fat in the liver and is the leading cause of chronic liver disease [1]
An accumulating number of animal and human studies suggest a compelling role for gut microbiota in NAFLD, which is both transmitted by gut microbiota and reversed by a combination of ciprofloxacin and metronidazole antibiotics in animal models [4]
NAFLD is associated with dysbiosis of the gut microbiota, which is thought to lead to increased gut permeability, and abnormal choline and bile acid metabolism, leading to inflammation and increased hepatic fat accumulation [5]
Summary
Non-alcoholic fatty liver disease (NAFLD) is defined by the pathological accumulation of fat in the liver and is the leading cause of chronic liver disease [1]. NAFLD encompasses a spectrum of diseases ranging from simple fatty liver (steatosis) through to non-alcoholic steatohepatitis (NASH), which, in turn, leads to fibrosis, irreversible cirrhosis and, hepatocellular carcinoma (HCC). NAFLD is associated with dysbiosis of the gut microbiota, which is thought to lead to increased gut permeability, and abnormal choline and bile acid metabolism, leading to inflammation and increased hepatic fat accumulation [5]. Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss difficult to maintain. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD.
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