DOP020Serum micro- and nano-plastic burden as a risk marker for Crohn’s disease progression: a multi-omics discovery of gut microbiome–metabolite perturbations

Abstract Background Up to half of patients with Crohn’s disease (CD) progress to disabling complications despite advanced therapies, with environmental exposures implicated as modifiers of disease course1. Micro- and nano-plastics (MNPs) are newly recognized ubiquitous contaminants capable of disrupting gut barrier and immune function in preclinical models2, yet no prospective human data link systemic MNP levels and its microbiome–metabolite correlates to CD progression. Methods In this two-center prospective study, serum levels of 11 MNP polymers were quantified using pyrolysis–gas chromatography–mass spectrometry in 241 CD patients and 43 healthy controls (HCs). Cross-sectional analyses compared serum MNP burden between CD and HCs and evaluated its associations with disease activity, behavior (B1 vs B2/B3), and inflammatory markers. CD patients with B1 behavior and no prior intestinal resection (n = 167) was prospectively followed (mean, 27.0±10.3 months) for composite progression outcomes. Multivariable Cox models assessed the association of baseline MNP burden with progression, adjusting for clinical risk factors. A multi-omics subset underwent fecal 16S/metagenomic sequencing and serum/fecal metabolomics to identify MNP-linked microbiome–metabolite signatures. Network and mediation analyses explored potential pathways in MNP-related progression. Results Serum MNP levels were significantly higher in CD than HCs (total: 90.7±33.7 vs 32.8±12.5 µg/g, p0.001), with PS, PE, PP, PVC and PA66 detected in all participants. Elevated total MNPs correlated with more severe endoscopic/MRE inflammation (r≈0.15–0.45, p0.05) and with stricturing/penetrating behavior (B2/B3 vs B1; OR 2.65, 95%CI 1.41–5.11). During follow-up, high total MNP exposure was associated with more frequent progression (45.7% vs 25.8%) and shorter progression-free survival (log-rank p = 0.011). Total MNPs independently increased progression risk (HR 2.95, 95%CI 1.57–5.57; per 1-SD increase HR 1.30, 95%CI 1.06–1.59), with similar estimates for PVC. Multi-omics analysis tied high MNP burden to enriched several Streptococcus/Bacteroides species, depleted Ruminococcaceae/Clostridiales taxa, and altered triacylglycerol- and amino acid–related pathways. Mediation analysis indicated that genus GCA-900066575 and triacylglycerol-related metabolites partially mediated MNP-disease progression relationship (q = 0.016 and q = 0.044). Conclusion Elevated serum MNP levels conferred a nearly 3-fold risk of disease progression in CD and mechanistically tied to a unique microbiome-metabolite signature. These findings support serum MNP assessment as a promising environmental marker to refine risk stratification and guide preventive strategies in CD management. References: 1.Estevinho MM, Lodeiro C, Vidal A, et al. Emerging role of environmental pollutants in inflammatory bowel disease risk, outcomes and underlying mechanisms. Gut. 2025;74(3):477-486. doi:10.1136/gutjnl-2024-332523 2.Hu L, Zhao Y, Xu H. Trojan horse in the intestine: a review on the biotoxicity of microplastics combined environmental contaminants. J Hazard Mater. 2022;439:129652. doi:10.1016/j.jhazmat.2022.129652 Conflict of interest: Huang, Lili: No conflict of interest Zheng, Weikai: No conflict of interest Wang, Yejun: No conflict of interest Feng, Shi-Ting: No conflict of interest Li, Xuehua: No conflict of interest