Protective effect of xylo-oligosaccharides on mice with fatty liver induced by high-fat diet and related mechanisms

Abstract

Objective To investigate the protective effect of xylo-oligosaccharides on mice with fatty liver induced by high-fat diet and related mechanisms. Methods A total of 40 male C57/BL6J mice, aged 5 weeks, were randomly divided into low-fat diet control group (LFD group), high-fat diet model group (HFD group), high-fat diet+low-dose xylo-oligosaccharide intervention group (XOS.L group), and high-fat diet+high-dose xylo-oligosaccharide intervention group (XOS.H group), with 10 mice in each group. The mice in the LFD group were fed a low-fat diet containing 10% fat, and those in the HFD group were fed a high-fat diet containing 60% fat; in addition to the treatment in the HFD group, the mice in the XOS.L group were given xylo-oligosaccharides at a dose of 0.35 g/kg by gavage once a day, and those in the XOS.H group were given xylo-oligosaccharides at a dose of 1.0 g/kg by gavage once a day; the mice in the LFD group and the HFD group were given an equal volume of normal saline by gavage. At the end of week 16, blood, liver tissue, and fecal samples were collected from each group of mice; the serum levels of alanine ami-notransferase (ALT), aspartate aminotransferase and triglyceride (TG) were measured; HE staining and oil red O staining were used to perform a histological evaluation of the liver; 16S rRNA microbial sequencing technology and metabolomics were used to measure the changes in fecal gut microbiota and metabolites. Results compared with LFD group, the HFD group showed significant steatosis of the liver, disturbances in various metabolites including arachidonic acid and linoleic acid (LA), significant increases in the abundances of the pathogenic bacteria such as Faecalibaculum, Bacteroidaceae, and significant reductions in the abundances of the probiotic bacteria such as Ruminococcaceae, Bacteroides. Compared with the HFD group, the XOS.H groups showed a significant improvement in liver steatosis and the abundances of related microbiota such as Ruminococcaceae and Actinobacteria, significant reductions in liver SAF scores and the enrichment intensities of the proinflammatory metabolites such as Prostaglandin H2, and significant increases in the enrichment intensities of the metabolites such as Prostaglandin D2, LA, and docosahexaenoic acid. Conclusion Xylo-oligosaccharides can significantly improve liver steatosis, gut microbiota dysbiosis, and metabolite disturbances induced by high-fat diet in mice, possibly by regulating the gut microbiota to interfere with the metabolic pathways such as arachidonic acid and LA.

Keywords

• oligosaccharides|prebiotics|non-alcoholic fatty liver disease|gastrointestinal microbiome|lipid metabolism|metabolic networks and pathways