S675 Antibiotic Exposure and Colorectal Cancer Risk: What Does the Microbiome Say?

Introduction: The incidence of early-onset colorectal cancer (CRC) has been rising. This sparked interest in modifiable risk factors. Antibiotics are known to alter gut microbiota composition, disrupt microbial diversity and promote inflammation. This narrative review synthesizes current evidence on the association between antibiotic exposure and the risk of CRC, with a focus on microbiome-mediated mechanisms. Methods: A targeted literature search was conducted using PubMed and Embase to identify epidemiologic studies examining antibiotic use and CRC risk, and mechanistic studies exploring microbiome alterations. Large-scale cohort studies exploring the relationship between antibiotic use and CRC and in vitro/in vivo studies elucidating microbiome-related pathways were reviewed. Results: In a population-based study, Lu et al. (2022) reported a positive association between more frequent antibiotic use and proximal colon cancer (CC), and inverse association among women with rectal cancer. There was no association between CRC and antiseptics not affecting gut microbiota. McDowell et al. (2021) reported that CC risk was associated with antibiotic consumption, especially in the patients <50 years old; similarly, no association was found between rectal cancer and antibiotic consumption. Zhang et al. (2019) reported a dose dependent increase of CC with antibiotic use, especially antibiotics with anti-anaerobic activity. An inverse association was detected between antibiotic use and rectal cancers. Liu et al. (2021) reported that 65 antibiotic resistance genes and 12 multidrug resistance genes were significantly enriched in patients with CRC. Mechanistic studies suggest that antibiotic-induced depletion of short chain fatty acid-producing bacteria (Faecalibacterium prausnitzii) and expansion of pro-inflammatory taxa (Fusobacterium nucleatum) may promote colorectal carcinogenesis by impairing gut barrier integrity, modulating immune responses, and enhancing tumorigenic pathways. Gaps remain regarding specific antibiotic classes, duration thresholds, and risk stratification based on host microbiome profiles. Conclusion: Antibiotic exposure is an emerging, potentially modifiable risk factor for CRC. This may be mediated in part by gut microbiome disruption. These findings underscore the need for antibiotic stewardship policies that consider long-term cancer risks, particularly in younger adults. Prospective studies integrating microbiome profiling are warranted to clarify causality and inform prevention strategies.