The role of gut microbiome composition in the IBD-CRC pathway: A retrospective study of 428 patients.

Abstract

3571 Background: The progression from inflammatory bowel disease (IBD) to colorectal cancer (CRC) is a significant clinical challenge, driven partly by inflammation and dysbiosis of the gut microbiome. This study aimed to investigate the relationship between gut microbiome composition, systemic inflammation, and CRC risk in patients with IBD. A secondary aim was to evaluate the potential protective effects of microbial diversity and specific bacterial taxa in mitigating CRC progression. Methods: This retrospective study analyzed data from 428 patients with a confirmed diagnosis of IBD, of whom 162 (37.9%) were diagnosed with CRC. Stool samples collected within one year of diagnosis were subjected to 16S rRNA gene sequencing to characterize microbial composition and diversity. Alpha and beta diversity indices were calculated to evaluate microbial richness and community dissimilarity, respectively. Specific microbial taxa, including Bacteroides fragilis, Escherichia coli, and Akkermansia muciniphila, were quantified due to their established roles in inflammation and carcinogenesis. Inflammatory biomarkers, including C-reactive protein (CRP), fecal calprotectin, IL-6, and IL-17 were measured from serum and stool samples. Clinical data, including demographics, disease duration, staging, and treatment history, were obtained from electronic medical records. Multivariate regression models were used to determine associations between microbial profiles, inflammatory markers, and CRC risk, adjusted for confounders such as age, sex, BMI, and immunosuppressive therapy. Results: Patients with CRC demonstrated reduced gut microbial diversity compared to IBD patients without CRC (Shannon Index: 2.3 ± 0.4 vs. 3.1 ± 0.5; p < 0.001). Dysbiosis in CRC patients was marked by an overrepresentation of pro-inflammatory bacteria (Escherichia coli and Bacteroides fragilis) and a depletion of protective taxa (Akkermansia muciniphila and Faecalibacterium prausnitzii). Pro-inflammatory biomarkers, including CRP (14.2 ± 3.6 mg/L vs. 6.7 ± 2.1 mg/L; p < 0.001) and fecal calprotectin (378.5 ± 85.2 µg/g vs. 215.3 ± 64.7 µg/g; p < 0.001), were elevated in patients with CRC. Regression analyses revealed that reduced microbial diversity (OR: 2.87, 95% CI: 1.92–4.28) and the presence of specific pathogenic taxa (Bacteroides fragilis: OR: 3.12, 95% CI: 2.03–4.79) were independently associated with increased CRC risk. Conversely, patients with higher relative abundances of Akkermansia muciniphila exhibited lower levels of inflammation and reduced CRC risk (OR: 0.52, 95% CI: 0.35–0.76), likely due to its role in maintaining mucosal integrity and modulating immune responses. Conclusions: This study underscores the critical role of gut microbiome composition in the IBD-CRC pathway, and highlights the need for microbiome-targeted interventions to prevent CRC progression in patients with IBD.