Abstract
ScopeAs a result of the obesity epidemic, the prevalence of non‐alcoholic steatohepatitis (NASH) is increasing. No drug is approved for the treatment of NASH. In this study, the effect of a nutritional supplement, Mastiha or Chios mastic gum, on metabolic and histological parameters and on the gut microbiome in mice with NASH and fibrosis was investigated.Methods and resultsAdvanced NASH was induced by feeding C57BL/6J mice a diet rich in fat, sucrose, and cholesterol for 41 weeks. After randomization, animals received the NASH‐inducing diet with or without 0.2% (w/w) Mastiha for a further 8 weeks. Disease activity was assessed by liver histology and determination of plasma transaminase activities. Fecal microbiota DNA extraction and 16S rRNA amplicon sequencing were used to determine the composition of the gut microbiome.Mastiha supplementation led to a significant reduction in circulating alanine aminotransferase (ALT) activity, improvement in hepatic steatosis and collagen content, and a reduction in NAFLD activity score. Furthermore, it resulted in a partial but significant recovery of gut microbiota diversity and changes in identity and abundance of specific taxa.ConclusionThis is the first study demonstrating an improvement in disease activity in mice with advanced NASH with fibrosis by a diet containing Mastiha.
Highlights
Nonalcoholic fatty liver disease (NAFLD) represents a wide spectrum of liver abnormalities including hepatic steatosis, non-alcoholic steatohepatitis (NASH) characterized by lobular inflammation and hepatocyte ballooning, and liver fibrosis
Based on the need for safe and efficacious therapy for NAFLD/NASH and the properties of Mastiha, we have investigated the effects of this resin on metabolic parameters, microbial diversity, hepatic pathology, and NAFLD activity in a biopsy-confirmed mouse model of advanced NASH with fibrosis
The effect of Chios Mastic Gum, administered orally as part of the diet (0.2%), was investigated in a chronic study in mice with diet-induced obesity and advanced NASH with fibrosis induced by long-term feeding with a diet rich in fat, fructose and cholesterol.[22,23]
Summary
Nonalcoholic fatty liver disease (NAFLD) represents a wide spectrum of liver abnormalities including hepatic steatosis, non-alcoholic steatohepatitis (NASH) characterized by lobular inflammation and hepatocyte ballooning, and liver fibrosis. Genetic predisposition and multiple “hits” such as insulin resistance, adipose tissue hormones, dietary factors, gut microbiota, or epigenetic factors determine the likelihood of progression from simple hepatic steatosis, a comparably benign condition, to advanced stages of NASH and fibrosis.[9]. Pleiotropic mechanisms simultaneously targeting several pathways playing a role in NASH development may have a higher probability of preventing the progression of this multifactorial disease. Natural food supplements such as vitamin E, omega-3 fatty acids, phenolic compounds, and other phytochemicals with a broad spectrum of activities are currently under investigation as potential non-pharmacological approaches in NAFLD.[10,11]. Based on the need for safe and efficacious therapy for NAFLD/NASH and the properties of Mastiha, we have investigated the effects of this resin on metabolic parameters, microbial diversity, hepatic pathology, and NAFLD activity in a biopsy-confirmed mouse model of advanced NASH with fibrosis
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