Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State

Hong Lin, Yanpeng An, Fuhua Hao, Yulan Wang, Huiru Tang, Hong Lin, Yanpeng An, Fuhua Hao, Yulan Wang, Huiru Tang

Abstract

Obesity resulting from interactions of genetic and environmental factors becomes a serious public health problem worldwide with alterations of the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. To understand the contributions of gut microbiota to obesity development, we analyzed dynamic alterations in fecal metabonomic phenotype using NMR and fecal microorganism composition in rats using pyrosequencing technology during the high-fat diet (HFD) feeding for 81 days (pre-obesity state). Integrated analysis of these two phenotypic datasets was further conducted to establish correlations between the altered rat fecal metabonome and gut microbiome. We found that one-week HFD feeding already caused significant changes in rat fecal metabonome and such changes sustained throughout 81-days feeding with the host and gut microbiota co-metabolites clearly featured. We also found that HFD caused outstanding decreases in most fecal metabolites implying enhancement of gut absorptions. We further established comprehensive correlations between the HFD-induced changes in fecal metabonome and fecal microbial composition indicating contributions of gut microbiota in pathogenesis and progression of the HFD-induced obesity. These findings provided essential information about the functions of gut microbiota in pathogenesis of metabolic disorders which could be potentially important for developing obesity prevention and treatment therapies.

Figures

Figure 1. HFD-induced dynamic changes in the…
Figure 1. HFD-induced dynamic changes in the fecal metabonome against controls with the Pearson correlation coefficients from OPLS-DA color-coded.
The red cells indicated the HFD-induced significant metabolite level increases whereas blue ones indicated decreases. UDPG: uridine diphosphate glucose; TMA: trimethylamine; DMA: dimethylamine; D-GlcNAc: N-Acetyl-D-glucosamine; 4-HPA: 4-hydroxyphenylacetate.
Figure 2. HFD-induced significant gut microbial changes…
Figure 2. HFD-induced significant gut microbial changes against controls in the (a) family and (b) genus levels, respectively, at day 7, 28, 56 and 81 post treatments.
The changes at each time-point were color-coded with values of 1-p where p-values were from the Student’s t-test or Kruskal-Wallis test. The red cells indicated the HFD-induced significant elevations of microbes whereas the blue ones indicated decreases. The white cells indicate the microbes with no significant inter-group differences.
Figure 3. Correlations for the significantly changed…
Figure 3. Correlations for the significantly changed fecal metabolites and microbial genera with the respective hierarchical clustering.
The correlation coefficients between specific fecal metabolites and certain bacterial genera were color-coded with hot color (e.g., red) denoting positive correlations whereas the cool one (e.g., green) indicating negative ones. 4-HPA: 4-Hydroxyphenylacetate; TMA: Trimethylamine; DMA: Dimethylamine; UDPG: Uridine diphosphate glucose; D-GlcNAc: N-Acetyl-D-glucosamine.

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