The microbiome landscape of early-onset colorectal cancer: A systematic review.

e15646 Background: The rise of early-onset colorectal cancer (EOCRC, age < 50 years old) necessitates the examination of potential risk factors to enhance prevention and control strategies. Microbial dysbiosis has been hypothesized as a potential contributor, yet studies are limited. To guide future research, we systematically reviewed studies of the EOCRC microbiome, emphasizing methodological heterogeneities. Methods: We systematically reviewed available literature for microbiome studies involving EOCRC and synthesized findings according to comparison groups (healthy/later-onset CRC LOCRC), sample type (fecal /tumor), and analyses (taxonomic/metabolomic). Results: Collection, storage, extraction, and analytical methods varied across the 10 studies included out of 2073 studies. There were 377 unique EOCRC patients, of which most originated from China (193 EOCRC cases), the United States (52 EOCRC cases), and Japan (42 EOCRC cases). Six studies analyzed 224 unique EOCRC fecal samples (4 performed 16S, 5 performed WGSS, 4 performed metabolomic); five compared EOCRC against healthy individuals and five to LOCRC. Four studies utilized 153 unique EOCRC tumor samples (3 performed 16S, 1 performed WGSS, 1 performed metabolomic); two compared with tumor-adjacent normal tissue, one to colonic tissue of healthy individuals, and four to LOCRC. Among studies comparing fecal samples of EOCRC to healthy individuals, EOCRC exhibited increased levels of Fusobacterium and Escherichia-Shigella, known for metabolizing 5-Fluorouracil, while butyrate-producing taxa like Faecalibacterium, protective against CRC, were diminished; EOCRC also showed decreased lung-associated pathogens and Clostridium difficile, but increased oral pathogens. Among studies comparing fecal samples of EOCRC to LOCRC, EOCRC fecal samples were more abundant in oral/gastrointestinal pathogens, with varying findings on Fusobacterium nucleatum. Faecalibacterium prausnitzii was more abundant in EOCRC than LOCRC, whereas Escherichia-Shigella was less abundant. Fecal metabolomic studies displayed increased LPS-related pathways and bile acids in EOCRC compared to healthy individuals. Compared to tumor-adjacent normal tissues or colonic tissues of healthy individuals, EOCRC tumors were characterized by higher levels of Fusobacterium, Actinomyces, and Escherichia coli ( E. coli), fewer butyrate producers, and more Bacteroides fragilis. Conclusions: While data is limited and methodologies varied, emerging evidence suggests that EOCRC may have unique microbial signatures compared to both healthy individuals and LOCRC. This may signal unique pathogenesis for EOCRC and present potential for prevention, early detection, and intervention. It is essential to harmonize study methods and analytical approaches to advance understanding of the role of microbiome in EOCRC.