Alteration and the Function of Intestinal Microbiota in High-Fat-Diet- or Genetics-Induced Lipid Accumulation.

Diet and host genetics influence the composition of intestinal microbiota, yet few studies have compared the function of intestinal microbiota in the diet- or genotype-induced lipid deposition, which limits our understanding of the role of intestinal bacteria in metabolic disorders. The lipid accumulation in wild-type zebrafish fed with control (CON) or high-fat (HF) diet and two gene-knockout zebrafish lines ( or ) fed with control diet was measured after a 4-week feeding experiment. The intestinal microbiota composition of these groups was investigated using 16S ribosomal RNA (rRNA) gene sequencing (DNA-based) and 16S rRNA sequencing (RNA-based). The HF diet or deficiency of two genes induced more weight gain and higher triglyceride content in the liver compared with their control group. 16S rRNA gene sequencing (DNA-based) indicated the decreased abundance of in the HF group compared with CON, but there was no significant difference in bacterial α diversity among treatments. 16S rRNA sequencing (RNA-based) confirmed the decreased abundance of and the bacterial α diversity in the HF group compared with CON. Deficiency of or showed less change in microbiota composition compared with their wild-type group. Intestinal microbiota of each group was transferred to germ-free zebrafish, and the quantification of Nile red staining indicated that the intestinal microbiota of the HF group induced more lipid accumulation compared with CON, whereas intestinal microbiota of and zebrafish did not. The results showed that RNA-based bacterial sequencing revealed more bacterial alteration than DNA-based bacterial sequencing. HF diet had a more dominant role in shaping gut microbiota composition to induce lipid accumulation compared with the gene-knockout of or in zebrafish, and the transplant of intestinal microbiota from HF-fed fish induced more lipid deposition in germ-free zebrafish. Together, these data suggested that a high-fat diet exerted a more dominant role over the deletion of or on the intestinal bacterial composition, which corresponded to lipid accumulation.