High-Fat Diet Alters the Intestinal Microbiota in Streptozotocin-Induced Type 2 Diabetic Mice

Abstract

Intestinal microbiota is closely associated with various metabolic diseases such as type 2 diabetes (T2D), and microbiota is definitely affected by diet. However, more work is required to gain detailed information about gut metagenome and their associated impact with diet in T2D patients. We used a streptozotocin-high-fat diet (HFD) to induce a T2D mouse model and investigated the effect of standard chow diet and HFD on the composition and function of gut microbiota. We found that a HFD could worsen the diabetes status compared with a standard diet. 16S rRNA gene sequencing revealed that a HFD caused a large disturbance to the microbial structure and was linked to an increased ratio of Firmicutes to Bacteroidetes. A HFD increased the bacteria of the Ruminococcaceae and Erysipelotrichaceae family and decreased the bacteria of S24-7 and Rikenellaceae. Meanwhile, a HFD decreased the abundance of Parabacteroides distasonis and Eubacterium dolichum, both of which have previously been reported to alleviate obesity and metabolic dysfunctions. Moreover, PICRUSt-predicted KEGG pathways related to membrane transport, lipid metabolism, and xenobiotics biodegradation and metabolism were significantly elevated in HFD-fed T2D mice. Our results provide insights into dietary and nutritional approaches for improving host metabolism and ameliorating T2D.

Keywords: 16S rRNA; gut microbiota; high-fat diet; streptozotocin; type 2 diabetes.

Figure 1

The experimental design and type 2 diabetes (T2D) mouse model. (A) Mouse experiment, 6-week-old C57BL/6 male mice (n = 50) were fed on a standard chow diet for one week, then injected with multiple low doses of streptozotocin (STZ) and fed on a high-fat diet (HFD) to obtain T2D mice. T2D mice received chow or HFD for four consecutive weeks. (B) Boxplot of body weight and fasting blood glucose in mice (n = 50) at the time point of week 1 and week 2. (C) Boxplot of fasting blood glucose in chow-fed T2D mice (Chow, n = 23) and HFD-fed T2D mice (HFD, n = 23) at week 6. *** denotes p < 0.001.

Figure 2

Alpha-diversity of the gut microbiota in two groups. Chao1, ACE, and Shannon indices were compared between chow-fed (n = 23) and HFD-fed (n = 23) T2D mice. *** p < 0.001, “ns” indicates no significance.

Figure 3

The structure of gut microbiota in two groups of mice. (A) PCoA based on weighted UniFrac distance of the OTUs abundance. The contributions of principal coordinate 1 (PC1) is on the X-axis and 2 (PC2) is on the Y-axis. (B) Bacterial taxonomic profiling at the phylum level among individuals is shown. Green bar represents chow samples, n = 23; red bar represents HFD samples, n = 23. (C) Boxplot of the relative abundance of Bacteroidetes and Firmicutes in samples from chow (n = 23) and HFD group (n = 23). *** denotes p < 0.001.

Figure 4

Species that significantly differ in abundance between chow group and HFD group. * FDR < 0.05, ** FDR < 0.01, *** FDR < 0.001, FDR-controlled Wilcoxon rank-sum test. The species names are colored according to significant differences: green, enriched in chow group; red, enriched in HFD group.

Figure 5

KOs and modules in samples of chow and HFD group. (A) PCA of the KO profile between the two groups. Chow samples, n = 23 (green); HFD samples, n = 23 (red). (B) Differentially modules between chow and HFD. Reporter score ≤ −1.96, blue color; reporter score ≥ 1.96, red color.