Alcohol consumption and colorectal carcinogenesis: an exploration of the gut microbial pathway as a potential mediator

Alcohol consumption is one of the major risk factors of colorectal cancer (CRC), yet the mechanisms underlying this relationship, particularly the role of gut microbes, are not fully understood. To study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions. Screening participants with a positive faecal immunochemical test at ages 55–77 were eligible for the CRCbiome study. Alcohol intake was assessed using a validated, semi-quantitative food frequency questionnaire and linked with shotgun metagenome based gut microbial profiles to study associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis. Of 1468 participants with dietary data, 414 were diagnosed with advanced lesions. Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend = 0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in α- and β-diversity, and differentially abundant bacteria. A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria. Alcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions. Trial registration: The BCSN is registered at clinicaltrials.gov (National clinical trial (NCT) no. 01538550).