Whole Metagenome Sequencing of colo-rectal cancer in Lynch Syndrome Patients

We performed whole gut metagenomic analysis in 17 Lynch syndrome (LS) families, including colorectal cancer (CRC) patients and their healthy first-degree relatives (Controls). Since bacteria are organized into different networks within the microbiota, we compared related network structures in patients and controls. Experimental Design: Fecal prokaryote DNA was extracted prior to colonoscopy for whole metagenome. We characterized bacteria taxonomy using the Diamond/MEGAN6 pipeline and performed differential abundances using the Shaman website. We constructed networks using SparCC inference tools and validated the construction's accuracy by performing qPCR on selected bacteria Results: Significant differences in bacterial communities in LS-CRC patients were identified, with an enrichment of virulent bacteria and a depletion of symbionts compared to their first-degree relatives. The main bacterial network structures, constructed based on bacteria-bacteria correlations in CRC (pilot study) and in precancerous patients (validation-study, data not deposited here), showed a different pattern than in controls. It was characterized by virulent/symbiotic co-exclusion in both studies and illustrated (validation study) by a higher Escherichia/Bifidobacterium ratio, as assessed by qPCR. Conclusions: Enhanced fecal virulent/symbiotic bacteria ratios influence bacterial network structures. As an early event in colon carcinogenesis, these ratios can be used to identify asymptomatic LS individual with a higher risk of CRC