The purpose of this study was to explore the difference and association between intestinal microbiota and plasma metabolomics between type 2 diabetes mellitus (T2DM) and normal group and to identify potential microbiota biomarkers that contribute the most to the difference in metabolites. Methods: Six male ZDF model (fa/fa) rats were fed by a Purina #5008 Lab Diet (crude protein 23.5%, crude fat 6.5%) for 3 weeks and their age-matched 6 ZDF control (fa/+) rats were fed by normal rodent diet. Their stool and blood samples were collected at 12 weeks. To analyze the microbial populations in these samples, we used a 16S rRNA gene sequencing approach. Liquid chromatography-mass spectrometry (LC-MS) followed by multivariate statistical analysis was applied to the plasma metabolites profiling. Correlation analysis of them was calculated by Pearson statistical method. Results: Twelve potential biomarkers of intestinal microbial flora and 357 differential metabolites were found in ZDF fa/fa rats, among which there are three flora that contributed the most to the perturbation of metabolites, including genus Phocea, Pseudoflavonifractor and species Lactobacillus intestinalis. Conclusion: Our study demonstrates the alterations of the abundance and diversity of the intestinal microbiota and the perturbation of metabolites in ZDF rats (fa/fa). We found three potential biomarkers of intestinal microbiota that may lead to perturbation in plasma metabolites. This may prompt new pathogenesis of obesity-related T2DM, but we also need to study further about the causal relationship between intestinal microbe and T2DM, so as to find the target of T2DM treatment or preventive measures.

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Type 2 diabetes mellitus (T2DM) is a burdensome global disease. In-depth understanding of its mechanism will help to optimize diagnosis and treatment, which reduces the burden. Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease. In the past two decades, the study of multi-omics on T2DM-related intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs. The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies. The use of metagenomics, 16S RNA sequencing, and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions. Lipidomics combined with other “omics” has characterized lipid metabolism disorders in T2DM. The combined application and cross-validation of multi-omics can screen for dysregulation in T2DM, which will provide immense opportunities to understand the mechanisms behind T2DM.

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