Interactions between the cecal microbiota and non-alcoholic steatohepatitis using laying hens as the model

Chronic liver disease has caused increasing numbers of deaths worldwide. Fatty liver hemorrhagic syndrome, one of the chronic liver diseases in laying hens, has great similarity to non-alcoholic fatty liver disease (NAFLD) in humans. It is characterized by the pathological accumulation of liver fat. Non-invasive techniques are needed for early identification of fibrosis. As primary de novo lipogenesis in the liver of chicken is similar to that of humans, mature chicken is an ideal animal model for the understanding of NAFLD. This study was aimed to evaluate the relationships between gut microbiota and natural chronic liver disease (i.e., non-alcoholic steatohepatitis [NASH] and fibrosis stages) in a well-characterized laying hen population. One hundred 20-wk-old Hy-Line Brown laying hens were used and fed with basal diets until 52 wk of age. At the end of the experiment, birds were killed for sampling blood, liver, and cecal contents, and then classified by liver histology measurement into different groups. We investigated microbial community structure of cecum using 16S rRNA gene sequencing. Subjects in stage 0 fibrosis without NASH were classified as low NAFLD (Group A), subjects in stage 1-2 fibrosis with mild to moderate NASH were defined as low NASH (Group B), and subjects in stage 3 fibrosis were defined as severe NASH (Group C). The abundance of Firmicutes was reduced in Groups B and C (P < 0.001), whereas opposite results were observed for the abundance of Bacteroidetes. Additionally, the families Bacteroidaceae, Ruminococcaceae Lachnospiraceae, and lactobacillae were significantly different between groups of differing fibrosis stages (P < 0.001), driven entirely by alterations of Bacteroides and lactobacillus and lachnospiraceae genera (P < 0.001), were observed. Results indicated that cecal dysbiosis was linked with the severity of fibrosis and NASH; importantly, increased levels of serum AST, alkaline phosphatase, and uric acid were accompanied with liver fibrosis and NASH severity. Collectively, these data highlight the role of gut-liver axis and associations between the gut microbiota and fibrosis and NASH severity.