Luminal and Tumor-Associated Gut Microbiome Features Linked to Precancerous Lesions Malignancy Risk: A Compositional Approach

SIMPLE SUMMARY: Studies of gut microbiome in patients with colorectal cancer (CRC) have shown strong alterations of its community structure. Identification of the early signs of changes may allow us to predict the risk of CRC using microbiome and improve the prognosis for such patients. The aim of our study was to evaluate the microbiome composition of luminal and tumor-associated microbiomes in patients with precancerous lesions and early forms of colon cancer. We found microbiome composition to be associated with many characteristics of the lesions. Among them, the findings related to luminal samples are of particular value due to the low invasiveness of the sample collection. Our results expand understanding of the microbiota involvement in triggering malignancy and contribute to the development of early-stage colon cancer diagnostics. ABSTRACT: Colorectal cancer is the third most commonly 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 colorectal cancer 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 profiled using high-throughput 16S rRNA sequencing. We showed that the microbiome differences between stool and biopsy samples can be to a high extent computationally corrected. Compositionality-aware statistical analysis of microbiome composition revealed its associations with the number of lesions, lesion type, location and malignization pathway. A major determinant of precancerous lesions malignancy risk—the number of lesions—was positively associated with the abundance of H(2)S-producing taxa. Our results contribute to the basis for developing early non-invasive colorectal cancer diagnostics via identifying microorganisms likely participating in early stages of cancer pathogenesis.