Transcriptome analysis of grass carp provides insights into disease-related genes and novel regulation pattern of bile acid feedback in response to lithocholic acid

Abstract

Gut microbiota and its metabolites affect lipid metabolism and liver health. Grass carp (Ctenopharyngodon idellus) often suffers from functional disorders of liver and gallbladder, which is usually accompanied by accumulation of lipids in the liver. Here we studied liver transcriptome and microbial fluctuation in the gut in response to dietary lithocholic acid (LCA; a metabolite of gut microbiota) supplementation in grass carp. A total of 1802 differentially expressed genes (DEGs) were identified between LCA and Control groups according to the liver transcriptome analysis. Of these DEGs, 8 nonalcoholic fatty liver disease-related genes were all upregulated, and 11 of 12 cancer related genes were upregulated in the LCA group. We also found significantly upregulated bile acid receptor, hepatocyte nuclear factor 4-beta (HNF4B), in the LCA group. The red oil O staining of liver showed a higher abundance of lipid droplets in the LCA group. LCA also changed the composition of gut microbiota, with increasing proportion of Proteobacteria and Firmicutes, whereas Fusobacteria decreased. Co-occurrence between DEGs and microbial taxa was mainly identified between signal transduction and genetic information processing-related genes and Proteobacteria and Firmicutes taxa. Overall, our results elucidate the effects of LCA on liver and gut microbiota in fish, and suggest a novel pattern of bile acid feedback in grass carp. These results contribute to our understanding of the interplay between gut microbiota and liver diseases in fish, and offer insights into putative treatments of liver diseases in grass carp.