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Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial

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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.

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Acknowledgements

The authors would like to thank all of the individuals who volunteered their time to participate and contribute to this study. The authors also thank Matt Workentine, Faculty of Veterinary Medicine, University of Calgary, for his technical assistance with 16S sequencing analysis.

Funding

This work was supported by a research grant from the Canadian Institutes of Health Research (MOP-136889) and a University of Calgary Seed Grant. MRB was supported by Alberta Innovates Health Solutions (AIHS) and an Honorary Izaak Walton Killam Doctoral Scholarship.

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Authors and Affiliations

  1. Department of Kinesiology and Physical Education, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada

    Marc R. Bomhof

  2. Faculty of Kinesiology, University of Calgary, 2500 University Drive NW, Calgary, AB, T2N 1N4, Canada

    Marc R. Bomhof & Raylene A. Reimer

  3. Department of Health and Physical Education, Mount Royal University, 4825 Mount Royal Gate SW, Calgary, AB, T3E 6K6, Canada

    Jill A. Parnell

  4. International Microbiome Centre, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada

    Hena R. Ramay

  5. Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada

    Pam Crotty, Kevin P. Rioux, Saumya Jayakumar & Maitreyi Raman

  6. Immunology and Infectious Diseases, Department of Microbiology, 1863 Health Sciences Centre, 3330 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada

    Kevin P. Rioux

  7. Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK

    Chris S. Probert

  8. Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada

    Raylene A. Reimer

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  1. Marc R. Bomhof
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  2. Jill A. Parnell
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  4. Pam Crotty
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  9. Raylene A. Reimer
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Contributions

MRB executed the study, collected data, analyzed data, and prepared the manuscript; JAP designed the study and obtained funding; HRR analyzed 16S gut microbiota sequencing data; PC collected data; KPR, SJ, and MR designed the study, collected data, and recruited participants; CSP performed VOC analysis; RAR designed the study, obtained funding and had final responsibility for the study. All authors had access to the study data and reviewed and approved the final manuscript.

Corresponding author

Correspondence to Raylene A. Reimer.

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Conflict of interest

MRB, JAP, HRR, PC, KPR, CSP, SJ, and MR declare no conflict of interest. RAR previously held a research grant from Beneo-Orafti, Inc., manufacturer of Orafti P95, for a project unrelated to this study.

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Bomhof, M.R., Parnell, J.A., Ramay, H.R. et al. Histological improvement of non-alcoholic steatohepatitis with a prebiotic: a pilot clinical trial. Eur J Nutr 58, 1735–1745 (2019). https://doi.org/10.1007/s00394-018-1721-2

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