IDDF2026-ABS-0512 Pro-inflammatory role of polypropylene in inflammatory bowel disease: mechanisms and implications

Background Microplastics are pervasive environmental contaminants that have been detected in natural ecosystems, the food chain and human tissues, raising growing concern about their potential health effects. The pathogenesis of inflammatory bowel disease (IBD) remains incompletely understood, and the impact of microplastic exposure on IBD has not been defined. Methods Intestinal specimens from patients with Crohn’s disease (CD) undergoing surgery were analysed for microplastic deposition (IDDF2026-ABS-0512 Figure 1(a) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). To investigate the effects of microplastics on intestinal inflammation, two murine models were employed: dextran sulfate sodium (DSS)-induced colitis (IDDF2026-ABS-0512 Figure 1(d) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling) and IL-10 knockout (KO) spontaneous enteritis (IDDF2026-ABS-0512 Figure 1(l) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). Mice were orally administered Polypropylene microplastic (PP-MPs) of two different particle sizes. Results In clinical specimens, PP-MPs were more abundant in inflamed intestinal tissue than in non-inflamed tissue (IDDF2026-ABS-0512 Figure 1(b,c) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). In the DSS model, exposure to 1μm PP-MPs (PP1) significantly aggravated colitis, as evidenced by increased mouse endoscopic index of colitis severity (MEICS) (IDDF2026-ABS-0512 Figure 1(g,i) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling) and disease activity index (DAI) scores (IDDF2026-ABS-0512 Figure 1(e) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling), marked colon shortening (IDDF2026-ABS-0512 Figure 1(f) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling) and more severe histopathological injury (IDDF2026-ABS-0512 Figure 1(h,j) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). Colonic transcriptomic profiling revealed upregulation of interferon-responsive genes, including Ifi44, together with enrichment of pathways related to antigen processing and presentation and phagosome. In IL-10-KO mice, exposure to 1μm PP-MPs (KO1) similarly exacerbated disease activity and colonic tissue injury (IDDF2026-ABS-0512 Figure 1(m,o) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). Single-cell transcriptomic analysis further demonstrated that microplastic exposure increased the proportions of monocytes, neutrophils and NK/T cells in the intestine, with a notable expansion of Ly6c+ monocytes and M1-like macrophages (IDDF2026-ABS-0512 Figure 1(t,u) Small-sized PP-MPs exacerbate intestinal inflammation and drive pro-inflammatory immune remodelling). Conclusions These findings show that small-sized microplastics consistently exacerbate intestinal inflammation across distinct experimental colitis models. This effect may be mediated through activation of interferon-associated inflammatory programmes, macrophage activation and M1-like macrophage polarisation. Our study identifies microplastics as a potential environmental risk factor for IBD progression and provides new evidence linking environmental particulate exposure to chronic intestinal inflammation.