Impact of Plasticizer on the Intestinal Epithelial Integrity and Tissue-Repairing Ability within Cells in the Proximity of the Human Gut Microbiome

Abstract

Toxicological research into the impact of plasticizer on different organs has been reported in the past few decades, while their effects on shifting the gut microbiota and immune cells homeostasis in zebrafish were only studied recently. However, studies on the impact of plasticizer on human gut microbiota are scarce. In this study, we co-incubated healthy human fecal microbiota with different concentrations of Di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DINP), analyzed microbial composition by 16S rDNA sequencing, and compared the influence of their derived microbiomes on the human enterocyte (HT-29) and murine macrophage (RAW264.7) cell lines. Microbial diversity is reduced by DEHP treatment in a dose-dependent manner. DEHP treatment reduced the phyla Firmicutes/Bacteroidetes ratio, while DINP treatment promoted Proteobacteria. Expressions of tight/adherens junction genes in HT-29 and anti-inflammatory genes in RAW264.7 were down-regulated by plasticizer-co-incubated microbiota derived metabolites. Overall, it is observed that selected plasticizers at high dosages can induce compositional changes in human microbiota. Metabolites from such altered microbiota could affect the tight junction integrity of the intestinal epithelium and upset macrophage differentiation homeostasis in proximity. Chronic exposure to these plasticizers may promote risks of dysbiosis, leaky gut or the exacerbation of intestinal inflammation.