Comparison of luminal and tumor-associated gut microbiome in patients with precancerous lesions and early forms of colon cancer: a compositional approach

Colorectal cancer (CRC) is the third diagnosed cancer worldwide. Human gut microbiome plays important roles in protecting against it, as well as contributing to its onset and progression. Identification of specific bacterial taxa associated with early stages of CRC may help develop effective microbiome-based diagnostics. For precancerous lesions, links of their characteristics to luminal and tumor-associated microbiome composition are to be elucidated.Paired stool and tumor brush biopsy samples were collected from 50 patients with precancerous lesions and early forms of colon cancer. Their microbial communities were investigated using high-throughput 16S rRNA sequencing. Statistical comparison of microbiome composition with lesion characteristics was performed using the "nearest balance", a novel compositionality-aware statistical method.There was a strong directional difference between the stool and biopsy samples reflected by a bacterial balance including 34 genera. We discovered multiple associations of overall microbiome composition and alpha diversity with the number of lesions, lesion type and location, with stronger effects for the biopsy samples. Compared to the left-sided lesions, the right-sided ones had reproducibly higher balance of 4 species (among them two Lachnospiraceae members) to 5 species (including Alistipes shahii and species from Parabacteroides and Bifidobacterium genera). The balance differentiating the small from the large lesions was partially overlapping. Probable pathway of malignization tended to be associated with 2 microbial cooperatives (co-abundance groups).Our results contribute to the basis for developing early non-invasive CRC diagnostics via establishing prognostic biomarkers and understanding the mechanisms of microorganisms participation in its pathogenesis.