Oral exposure to polyethylene microplastics exacerbates the effects of a Western-style diet on the digestive tract of adult male mice

Microplastic pollution is a growing global concern, yet the human health effects of exposure to microplastics, particularly in interaction with dietary factors, are not well understood. In this study, we investigated the impact of polyethylene microplastics (PE-MPs) on intestinal homeostasis in mice fed either a normal (ND) or Western (WD) diet for 90 days. Mice were orally exposed to PE-MPs (10 mg/kg body weight/day) throughout the experimental period. Under ND conditions, PE-MP exposure induced subtle changes in gut microbiota composition and short-chain fatty acid (SCFA) production, including a significant decrease in propionate, without overt intestinal inflammation. In contrast, under WD conditions, PE-MP exposure markedly exacerbated the diet-induced phenotype. WD-fed mice exposed to PE-MPs exhibited increased body weight gain, decreased expression of tight-junction related-genes and elevated faecal levels of the inflammatory marker lipocalin-2 and secretory IgA. These effects were accompanied by decreased abundances of Akkermansiaceae and Saccharimonadaceae, enrichment of Peptostreptococcaceae, and reduced caecal levels of propionate, isobutyrate, isovalerate and caproate. Together, these findings indicate that PE-MP exposure exacerbates WD effects, resulting in altered gut microbiota composition and metabolic activity, and increased intestinal inflammation. This study emphasises the importance of taking nutritional status into account when evaluating the toxicity of MPs and sheds new light on how this emerging class of food contaminant interacts with dietary stressors to shape host-microbiome relationships.