Combined exposure to microplastics and particulate matter induced intestinal inflammation and barrier dysfunction

Water and air pollution are implicated in the development of inflammatory intestinal diseases. However, the combined effects of simultaneous exposure to water and air pollutants on intestinal injury and their underlying mechanisms remain unclear. In this study, we investigate the role of microplastics (MP), representing water pollution, and particulate matter (PM), representing air pollution, in inducing intestinal inflammation, barrier dysfunction, and dysbiosis. To simulate combined air and water pollution exposure, we established a mouse model with daily gavage of microplastics (2 mg/kg) and intratracheal instillation of PM (10 mg/kg) four times over four weeks. Intestinal morphology was assessed using H&E and PAS staining. Tissue analysis revealed that MP and PM treatment altered mucin expression without significant structural deterioration. Moreover, intestinal reactive oxygen species (ROS) levels were significantly elevated in mice subjected to combined MP and PM exposure, as shown by in vivo imaging system (IVIS) analysis, consistent with malondialdehyde (MDA) levels assessed by the TBARS assay. This co-exposure increased ICAM-1 expression and reduced ZO-1 levels, indicating intestinal inflammation and barrier dysfunction. Oxidative stress was closely linked to endoplasmic reticulum (ER) stress and autophagy. MP and PM exposure elevated ER stress markers GRP78 and ATF6, along with autophagy-related proteins p62 and LC3B-II. Additionally, the combined exposure exacerbated intestinal dysbiosis in mice. These findings suggest that co-treatment with MP and PM amplifies oxidative stress, triggers ER stress and autophagy, and disrupts intestinal homeostasis, highlighting potential mechanisms of pollutant-induced intestinal injury. This work was supported by research grants from the National Science and Technology Council (NSTC 113-2320-B-005-012 - to T.C.L). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.