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

ABSTRACT: 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.

SUBMITTER: Qiao F

PROVIDER: S-EPMC8484964 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAccumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism.ResultsA high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet.ConclusionsThese results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

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

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