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 (cpt1b^–/– or pparab^–/–) 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 Proteobacteria 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 Proteobacteria and the bacterial α diversity in the HF group compared with CON. Deficiency of cpt1b or pparab 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 cpt1b^–/– and pparab^–/– 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 cpt1b or pparab 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 cpt1b or pparab on the intestinal bacterial composition, which corresponded to lipid accumulation.

饮食和宿主遗传学影响肠道微生物群的组成，但很少有研究比较肠道微生物群在饮食或基因型诱导的脂质沉积中的功能，这限制了我们对肠道细菌在代谢紊乱中作用的理解。用对照（CON）或高脂肪（HF）饮食和两种基因敲除斑马鱼线喂养的野生型斑马鱼的脂质积累（cpt1b^–/–或帕拉布^–/– ) 在 4 周的喂养实验后测量了用对照饮食喂养。使用 16S 核糖体 RNA (rRNA) 基因测序（基于 DNA）和 16S rRNA 测序（基于 RNA）研究了这些组的肠道微生物群组成。与对照组相比，HF 饮食或两种基因的缺乏导致肝脏中更多的体重增加和更高的甘油三酯含量。16S rRNA 基因测序（基于 DNA）表明变形菌HF 组与 CON 相比，细菌 α 多样性在处理之间没有显着差异。16S rRNA 测序（基于 RNA）证实了变形菌与 CON 相比，HF 组的细菌 α 多样性。缺乏cpt1b 或者 帕拉布与野生型组相比，微生物群组成的变化较小。将各组的肠道菌群转移到无菌斑马鱼中，尼罗红染色的定量表明，与 CON 相比，HF 组的肠道菌群诱导了更多的脂质积累，而cpt1b^–/–和帕拉布^–/–斑马鱼没有。结果表明，与基于 DNA 的细菌测序相比，基于 RNA 的细菌测序揭示了更多的细菌变异。与基因敲除相比，HF 饮食在塑造肠道微生物群组成以诱导脂质积累方面具有更大的作用。cpt1b 或者 帕拉布在斑马鱼中，从 HF 喂养的鱼中移植肠道微生物群会在无菌斑马鱼中诱导更多的脂质沉积。总之，这些数据表明高脂肪饮食对删除cpt1b 或者 帕拉布 对肠道细菌组成的影响，这与脂质积累有关。