Functional Characterization of Bacterial Strains Enriched in Colon Adenomas and Their Impact on Colonic Epithelial Cells

Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer-related mortality. It arises from the progressive accumulation of genetic and epigenetic alterations in the epithelial cells lining the colon or rectum, often evolving from precancerous lesions such as adenomatous polyps. Lifestyle factors—including diet, obesity, and physical inactivity—as well as hereditary predispositions contribute significantly to CRC risk. In recent years, increasing attention has been directed toward the role of the gut microbiota in colorectal cancer development and progression. The intestinal microbiota, a complex and dynamic community of microorganisms, is essential for maintaining gut homeostasis, immune function, and metabolic balance. Dysbiosis—an imbalance in microbial composition—has been linked to CRC through mechanisms such as chronic inflammation, production of carcinogenic metabolites, and modulation of host signalling pathways. Certain bacterial species have been identified as potentially pro-tumorigenic, while others may exert protective effects, highlighting the microbiota as both a risk factor and a promising target for prevention, diagnosis, and therapy in colorectal cancer. This study is based on the “Metabolic Population Hypothesis “, which proposes that distinct dysbiotic microbial communities can converge functionally to produce similar metabolic outputs, ultimately driving the same pathological outcome. In the context of colorectal cancer, this concept suggests that different configurations of the gut microbiota—though taxonomically diverse—may promote a pro-tumorigenic environment. These shared metabolic activities can promote chronic inflammation, epithelial damage, and genomic instability, contributing to drive early epithelial alterations, shifting normal mucosa toward a pre-neoplastic phenotype that can evolve into adenomas and ultimately colorectal cancer. The aim of this study is to metabolically and functionally characterize microbial populations enriched in colorectal adenomas. By integrating analyses of microbial composition with their metabolic potential and activity, the study seeks to identify key functional traits and pathways associated with adenoma-associated communities. In this study, we have identified adenoma associated mucosa preponderant bacterial strains and went on to evaluate their potential role in generating and promoting a pro-tumorigenic environment. We investigated these bacteria by assessing their impact on key cellular processes relevant to colorectal carcinogenesis. In particular, we evaluated their ability to induce DNA damage and modulate epithelial cell proliferation rates, both of which are critical features of early tumour development. In addition, we examined their effects on intestinal barrier integrity, including epithelial permeability and tight junction function. Finally, we explored their interactions with the host immune system, focusing on their capacity to trigger inflammatory responses or alter immune signalling pathways. Together, these analyses provide a comprehensive view of how adenoma-associated bacteria may influence multiple aspects of host physiology linked to disease progression.