Di-n-pentyl phthalate exposure alters intestinal structure and gut microbiota composition and characteristics in mice

Di-n-pentyl phthalate (DnPP), a ubiquitous plasticizer structurally analogous to the gut toxicant di-(2-ethylhexyl) phthalate (DEHP), poses environmental persistence and human exposure risks, yet its gastrointestinal toxicity remains poorly characterized. We hypothesized DnPP disrupts intestinal homeostasis via gut microbiota dysbiosis, mirroring mechanisms of other phthalates.

C57BL/6 mice (n = 10 per group) were orally gavaged with DnPP (1-100 mg/kg/d) for 21 days. Intestinal tissues and microbiota were analyzed using histomorphometry and metagenomic sequencing with functional annotation (GO/KEGG/CARD databases). Taxonomic and functional shifts were identified via Metastats and LEfSe (FDR < 0.05).

DnPP exposure induced dose-dependent villus degeneration (100 mg/kg/d, P < 0.05) and colon shortening (P < 0.01), accompanied by upregulated pro-inflammatory cytokines (IL-6, TNF-α) and downregulated tight junction proteins (ZO-1, occludin) in small intestinal and colonic tissues. Metagenomic analysis revealed tissue-specific dysbiosis: colonic samples showed Bacteroidota enrichment and Firmicutes depletion, while the small intestine exhibited increased Bacteroidota and Bifidobacterium. Functional analyses demonstrated reduced glycan/lipid metabolism pathways (P < 0.001) and elevated antibiotic resistance genes (CARD, P < 0.05).

DnPP disrupts mouse intestinal structure, triggers inflammation, reduces probiotic abundance, upregulates antibiotic resistance genes, and impairs gut microbiota metabolic capacities, highlighting non-negligible health risks for intestinal and systemic metabolism, as well as potential risks of metabolic and infectious diseases. These findings provide critical evidence for phthalate ester health hazard mechanistic studies.