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

PurposeIn 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.MethodsIn 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 (8g/day for 12weeks followed by 16g/day for 24weeks) or isocaloric placebo for 9months. 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.ResultsIndependent 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.ConclusionsIndependent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted.Clinical TrialThis trial was registered at Clinicaltrials.com as NCT03184376.