Blood Bacterial DNA Load and Profiling Differ in Colorectal Cancer Patients Compared to Tumor-Free Controls

SIMPLE SUMMARY: In colorectal cancer patients, epithelial barrier dysfunction can lead to increased intestinal permeability, and gut microbiome was found to vary compared to healthy subjects. We conducted a study to investigate whether bacterial translocation from gastrointestinal tract to bloodstream is associated to intestinal adenoma and/or colorectal cancer. In particular, an epidemiological and metagenomic approach was used to evaluate the relation of the bacterial DNA load and the bacterial taxonomic groups—assessed by 16S rRNA profiling—in blood with the risks of intestinal adenoma and colorectal cancer. These findings can confirm the presence of bacterial DNA in blood in healthy adults and serve as a basis to evaluate new non-invasive techniques for an early CRC diagnosis through the analyses of bacterial DNA circulating in peripheral blood. ABSTRACT: Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.