Effects of sterol regulatory element binding protein 1c deficiency on gut microbial composition in mice

Abstract

Objective To investigate the effects of sterol regulatory element binding protein 1c (SREBP1c) deficiency on the intestinal microbiota in mice. Methods SREBP1c knockout (SREBP1c-KO) mice were used as research objects, and the feces of homozygous SREBP1c-KO mice and wild-type littermates (WT) were collected. Subsequently, the fecal genomic DNA was analyzed by 16S rDNA sequencing. The differences of gut microbial composition between the SREBP1c-KO and WT mice were detected and compared using species taxonomy analysis, diversity index analysis, cluster analysis, and principal component analysis (PCA). Moreover, the discrepancies of liver lipid anabolism and intestinal barrier were also investigated between the 2 groups. Results Under conventional feeding, SREBP1c knockout had no significant effect on the body weight and total cholesterol (TC) content in the liver of mice, but notably decreased the content of triglyceride (TG) in the liver. α diversity index (Sobs index) analysis showed that the gut microbiota diversity of SREBP1c-KO mice was greatly lower than that of the WT counterparts (P < 0.01), and PCA analysis indicated that the gut microbial composition was different between the 2 groups of mice. At the phylum level, the ratio of Firmicutes to Bacteroides presented an upward trend in the intestine of SREBP1c-KO mice, but there was no statistical difference. At the genus level, as compared with the WT group, the relative abundance of Rikenella was significantly reduced in SREBP1c-KO mice (P < 0.05). Additionally, the expression levels of intestinal barrier associated genes Reg3γ and Occludin were obviously down-regulated in SREBP1c-KO mice. Conclusion The deletion of SREBP1c, an important regulator of lipid metabolism, reduces the diversity of intestinal microbiota and the relative abundance of Rikenella in mice, which may be related to the weakening of intestinal barrier.

Keywords

• sterol regulatory element binding protein 1c
• gut microbiota
• 16s rdna sequencing
• diversity
• intestinal barrier