Identificação de alterações taxonômicas no bacterioma fecal associado à pólipos e câncer colorretal: potenciais biomarcadores para diagnóstico precoce

Abstract

Colorectal cancer (CRC) is a disease of worldwide concern that has an established relationship with the intestinal microbiota. Most cases of sporadic CRC arise in patients with pre-malignant lesions in the colon called polyps, which are also influenced by the intestinal microbiota. In this study, we used shotgun metagenomic data to analyze the taxonomic diversity of bacteria present in fecal samples from 90 clinical individuals, including 30 control participants, 30 patients with polyps, and 30 with CRC. In individuals with CRC, our findings revealed a significant reduction in the abundance of taxa Lactobacillales (Order), Clostridiaceae (Family), and more specifically, the genera Faecalibacterium, Candidatus Arthromitus, and Ruminoccoccus. Clostridiaceae exhibited significantly lower abundance in the early stages of CRC. Additionally, the putative family Ruminococcaceae and the genus Desulfovibrio were found overrepresented in the bacteriome of CRC patients compared to the other groups, with a negative co-occurrence between Desulfovibrio and Faecalibacterium, suggesting a possible antagonistic relationship. Sulfate-reducing and/or oral cavity-related genera tended to be increased in the bacteriome of CRC and polyps, while the relative abundance of genera with anti-inflammatory, immunogenic, and butyrate-producing properties decreased. Furthermore, we identified taxonomic heterogeneity in the bacteriome of CRC patients linked to age, gender, tumor staging, and diabetes. The presence of dyslipidemia resulted in a significant increase in the abundance of the Streptococcaceae family in the bacteriome of control and polyp patients. We also observed an overrepresentation of the family Streptococcaceae in the bacteriome of other polyp patients, while the genus Lachnoclostridium was increased only in the group with polyp and without a family history of CRC, suggesting a possible influence of genetic components. Patients with polyps ≥ 1 cm also exhibited an increased abundance of the genus Ralstonia, along with a reduction in alpha diversity. These findings provide potential novel biomarkers for the diagnosis of polyps and CRC, as well as demonstrate the impact of host intrinsic factors on the establishment of the fecal bacteriome.