Marc R Bomhof1,2, Jill A Parnell3, Hena R Ramay4, Pam Crotty5, Kevin P Rioux5,6, Chris S Probert7, Saumya Jayakumar5, Maitreyi Raman5, Raylene A Reimer8,9. 1. Department of Kinesiology and Physical Education, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada. 2. Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada. 3. Department of Health and Physical Education, Mount Royal University, 4825 Mount Royal Gate SW, Calgary, AB, T3E 6K6, Canada. 4. International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada. 5. Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada. 6. Immunology and Infectious Diseases, Department of Microbiology, 1863 Health Sciences Centre, 3330 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada. 7. Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK. 8. Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada. reimer@ucalgary.ca. 9. Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. reimer@ucalgary.ca.
Abstract
PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.
RCT Entities:
PURPOSE: In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH. METHODS: In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota. RESULTS: Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease. CONCLUSIONS: Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted. CLINICAL TRIAL: This trial was registered at Clinicaltrials.com as NCT03184376.
Entities:
Keywords:
Gut microbiota; Non-alcoholic steatohepatitis; Oligofructose; Prebiotic
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