Genomic Map of Escherichia coli and Single Nucleotide Polymorphism Markers in Colorectal Cancer.

Gut microbial single nucleotide polymorphisms (SNPs) offer stable, specific genetic markers for disease diagnosis. Escherichia coli (E. coli), a dominant gut bacterium, is associated with colorectal cancer (CRC), but limited enteric reference genomes hinder SNP annotation in intestinal strains. Metagenomic sequencing profiled gut microbiota in 200 CRC patients and 200 healthy controls. The E. coli strain WDP was fully sequenced via PacBio single-molecule technology for genome assembly and functional annotation. Wilcoxon tests identified differentially abundant microbes, while Lasso regression models integrated microbial features (bacteria, viruses, virus-host pairs) and E. coli SNPs to predict CRC risk. E. coli abundance did not differ between groups, but genomic analysis revealed 7460 CRC-associated SNPs. The SNP-based model achieved superior accuracy (92.86% training, 93.33% testing, 84.00% validation) and AUC (0.986, 0.983, 0.913), outperforming models based on microbial abundances (e.g., Staphylococcus capitis, Zindervirus) or virus-host interactions. PacBio-generated E. coli genomic maps enable precise SNP annotation, establishing E. coli SNPs as highly accurate biomarkers for CRC risk prediction. This approach leverages microbial genetic stability to advance non-invasive early detection, offering a novel target for precision microbiome-based diagnostics.