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Nanoplastics exacerbate DSS-induced colitis via histone lactate axis

Ecotoxicology and Environmental Safety 2026
Shan Tian, Yugang Hu, Jinhui Zou, Nan Hao, Jian Liu, Ruixue Li, Jiao Li

Summary

New research in mice found that tiny plastic particles (nanoplastics) can make gut inflammation worse by changing how immune cells in the colon behave at a molecular level, worsening symptoms similar to ulcerative colitis. The plastics seem to alter energy processing in immune cells in a way that turns up inflammation, offering a possible explanation for how everyday plastic exposure might harm gut health. While this study was done in mice and cells, it adds to growing evidence that nanoplastic pollution deserves serious attention as a potential risk to human digestive health.

Polymers

Nanoplastic pollution is a serious global concern, which has caused great threat to the human health. However, the relationship between nanoplastic exposure and the development and progression of ulcerative colitis (UC) is still unknown. We established a chronic dextran sulfate sodium (DSS)-induced colitis model with exposure to polystyrene nanoplastics (PS-NPs) and evaluated disease severity, gut inflammation, and intestinal barrier function. The immune microenvironment was assessed using fluorescence multiplex immunohistochemistry (mIHC), while histone lactylation modification was analyzed via western blot and Cleavage Under Targets and Tagmentation (CUT&Tag). Additionally, lipopolysaccharide (LPS)-treated RAW264.7 cells were cultured and intervened to further investigate the molecular mechanism of PS-NPs in colitis. Continuous exposure to PS-NPs exacerbated gut inflammation and damage intestinal barrier function in DSS-induced colitis. PS-NPs exposure is closely correlated with increased macrophage infiltration, enhanced the glycolysis and up-regulated the histone H3 lactylation in macrophages. CUT&Tag analysis showed that PS-NPs influenced the expression of GART via histone H3K18la lactylation. Intervention in histone H3K18la lactylation significantly altered the expression of GART and levels of inflammatory factors in LPS-treated RAW264.7 cells. Downregulating GART expression reduced inflammatory factor levels in RAW264.7 cells treated with LPS plus PS-NPs. PS-NPs exposure exacerbates colitis by upregulating histone H3 lactylation. This study reveals a novel mechanism underlying nanoplastic-exacerbated intestinal injury and provides a direction for future risk assessment of nanoplastics.

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