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Background Emerging evidence suggests that environmental contaminants, such as microplastics (MPs), may accelerate colonic polyp progression by disrupting gut homeostasis. MPs have been detected in human stool and colonic tissue, raising concerns about their potential role in gastrointestinal diseases. This study investigates the presence and impact of MPs in polyps, exploring their association with gut dysbiosis and barrier dysfunction that may contribute to polyp-to-cancer progression.Methods Colonic tissues and stool from 35 healthy controls and 35 patients with colonic polyps were analysed for MPs using Laser Direct Infrared (LDIR) Chemical Imaging Spectroscopy with a spectral matching threshold >0.80. Gut microbiota composition was assessed by 16S rRNA amplicon sequencing. The ultrastructural integrity of epithelial junctions (tight junctions, adherens junctions, and desmosomes) was evaluated via transmission electron microscopy (TEM). Gene expression of proinflammatory cytokines and transmembrane proteins was measured using RT-qPCR.Results Polyp tissues and stool samples showed significantly higher levels of carcinogenic polyurethane (53.95±5.56) and polyvinyl chloride (5.48±2.42) respectively ( IDDF2026-ABS-0347 Figure 1). MPs found in colonic polyps were more solid and spherical with smaller height, width, area, and perimeter. Gut microbiome composition differed significantly between colonic polyp and healthy individuals, with reduced richness and evenness observed in polyp patients (p<0.05) (IDDF2026-ABS-0347 Figure 2). Both mucin-degrading bacteria (Parabacterioides_B_distasonis, Phocaeicola_A_vulgatus, Bacteroides_H_thetaiotaomicron) and mucin-producing bacteria (Blautia sp.) were enriched in polyps, indicating a dynamic microbial response to maintain mucosal homeostasis (IDDF2026-ABS-0347 Figure 3). Fusobacterium, a genus with known pathogenic potential, was frequently detected in polyp tissues. The presence of pathogenic bacteria corresponded with reduced propanoic acid levels (6.82±5.05; p<0.05) (IDDF2026-ABS-0347 Figure 4). TEM analysis revealed widened tight junctions (10.5±0.96nm), adherens junctions (20.38 ±1.98nm), and desmosomes (26.98±2.06nm) in polyp tissues (p<0.05), indicating epithelial barrier disruption (IDDF2026-ABS-0347 Figure 5). Furthermore, an immunosuppressive environment was evidenced by downregulation of IFN-γ and upregulation of CDH1 and CLDN1 in colonic polyps (IDDF2026-ABS-0347 Figure 6). Conclusions These findings suggest that MPs may influence gut microbiota composition and compromise epithelial barrier integrity, potentially contributing to precancerous changes in colonic polyps. The correlation between MP abundance in colonic polyp tissues and microbial dysbiosis underscores their potential role in colorectal cancer (CRC) development and the urgent need to clarify the underlying mechanisms linking MP exposures to CRC risk.Abstract IDDF2026-ABS-0347 Figure 1Abstract IDDF2026-ABS-0347 Figure 2Abstract IDDF2026-ABS-0347 Figure 3Abstract IDDF2026-ABS-0347 Figure 4Abstract IDDF2026-ABS-0347 Figure 5Abstract IDDF2026-ABS-0347 Figure 6