The mediating role of genes in the influence of intestinal flora on type 2 diabetes and the screening of diagnostic markers.

INTRODUCTION: The composition of intestinal flora affects the occurrence and development of type 2 diabetes to some extent, with dysregulation of the microbiome being a clinical manifestation of the disease. METHODS: The key intestinal flora with causal relationship to type 2 diabetes was obtained by mendelian randomization (MR) analysis. Meanwhile, differentially expressed genes (DEGs) were analyzed in the GSE76894 dataset and overlapped with causal genes. The differentially expressed causal genes were screened by machine learning, and diagnostic markers of type 2 diabetes were identified. We also analyzed the expression of diagnostic markers for different cell types using the single-cell data to provide a more reliable basis for disease diagnosis. RESULTS: The study identified 10 key intestinal flora that were causally linked to type 2 diabetes through MR analysis. Transcriptome-wide association study (TWAS) and cis-expression quantitative trait loci.(eQTL) MR analysis of type 2 diabetes identified 228 genes that were causally linked to type 2 diabetes (|Z score| > 1, P < 0.05). About 20 causal genes were selected by MR analysis of 228 genes and intestinal flora causally related to type 2 diabetes. The diagnostic markers screened by machine learning were verified by the area under the curve (AUC), the results were all >0.7, indicating good diagnostic efficiency. Single-cell analysis suggested that BEND7 was specifically high expression in the control group, and C1orf85 was specifically high expression in samples with type 2 diabetes. CONCLUSIONS: The study provided a solid theoretical basis for further understanding of the underlying mechanisms of type 2 diabetes pathogenesis and progression.