Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, responsible for approximately 0.90 million deaths in 2022. CRC can be categorized into two major types based on the anatomical location of the tumors. The proximal (right-sided) and distal (left-sided) colons possess anatomical, developmental, and physiological distinctions, including differences in embryonic origin, vascularization, neuronal supply, and microbial composition. These fundamental differences influence disease onset, progression, pathological features, and clinical outcomes. Right-sided CRC is consistently associated with poorer prognosis, greater resistance to treatment, lower survival rates, and a higher risk of recurrence compared to left-sided CRC.
Being a multifactorial disease, CRC is also linked to gut microbiome dysbiosis and is closely associated with pro-oncogenic bacterial strains, including Fusobacterium nucleatum, pks+ Escherichia coli, and enterotoxigenic Bacteroides fragilis. These bacteria contribute to tumorigenesis by producing toxins that damage epithelial integrity, promote inflammation, and induce DNA mutations. They often form invasive polymicrobial biofilms that enhance tumor progression, particularly in right-sided CRC, where such biofilms are more prevalent. Biofilm development is regulated by quorum sensing (QS), a bacterial communication system in which small signaling molecules coordinate the expression of virulence genes and interactions between species
The current project has focused on elucidating the role of QS in regulating polymicrobial biofilm formation by CRC-associated bacteria and on developing a probiotic strain capable of sensing these QS signals to identify and target pro-oncogenic biofilms. This approach is being explored as a potential alternative to antibiotics and natural probiotics, which show limited efficacy against biofilms. Targeting CRC-associated microbial biofilms may help limit biofilm-associated disease progression in CRC and reduce disease severity. Furthermore, if administered in the early stages of CRC, it could slow disease progression and prevent recurrence following treatment.
