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Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

ABSTRACT: Micro and nanoplastics (MNPs) are widespread contaminants of our environment and food web that can be absorbed by the intestine and distributed to most or all organs, and may cause significant toxicity and dysfunction. In our recent study, we investigated the toxicity and mechanisms underlying uptake and translocation of 26 nm carboxylated polystyrene MNPs (PS26C) using a combination of simulated digestion and a static, immortalized cell-based, three cell type (triculture) small intestinal epithelial model. Results revealed that PS26 caused minimal toxicity, and inhibitor studies revealed that uptake mechanisms included passive diffusion, phagocytosis, clathrin-mediated endocytosis (CME), and fast endophilin-mediated endocytosis (FEME). However, the triculture model is somewhat lacking in physiological relevance, and studies in a more relevant and accurate model are required to validate and expand upon those results. In the current study, we therefore employed a microfluidic intestine-on-a-chip model developed using primary human intestinal epithelial organoids from both healthy and Crohn’s disease donors, and primary human microvascular endothelial cells to evaluate the toxicological impacts and mechanisms effectuating uptake and translocation of 25 nm polystyrene shell-gold core tracer (quantifiable by ICP-MS) MNPs (AuPS25). As in our previous study, AuPS25 caused minimal toxicity after 24 h exposure in either the healthy or Crohn’s IOC model. RNAseq analysis of epithelial cell lysates identified only 9 dysregulated genes, which notably included downregulation of IFI6 (interferon alpha-induced protein 6), which has antiviral and negative innate immune regulatory functions in the intestine. Inhibitor studies revealed that AuPS25 uptake occurred by both passive and active mechanisms, including phagocytosis and/or macropinocytosis, and CME and/or FEME. Interestingly, uptake and translocation of AuPS25 was greater in healthy than in unstimulated Crohn’s disease epithelium.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285272 | GEO | 2025/06/18

REPOSITORIES: GEO

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Project description:M cells are the main site of bacterial translocation in the intestine. We used the in vitro M cell model to study the effect of the commensal bacteria; Lactobacillus salivarius, Eschericha coli and Bacteroides fragilis, on M cell gene expression. Bacterial translocation across the gut mucosa has traditionally been based on the detection of commensals in the mesenteric lymph node. Differential rates of commensal translocation have been reported in vivo, however fewer studies have examined translocation of commensals at the level of the gut epithelial M cell. In this study we employed an in vitro M cell model to quantify translocation of various bacteria. C2BBe1 cells were differentiated into M cells and the gene expression profile and transport kinetics of different bacterial strains, namely Lactobacillus salivarius, Escherichia coli, and Bacteroides fragilis, was assessed. For comparison with M cell uptake, the THP-1 monocytic cell line was used to analyze bacterial internalization and resulting cytokine production. The commensal bacterial strains were translocated across M cells with different efficiencies; E. coli and B. fragilis translocated with equal efficiency while L. salivarius translocated with less efficiency. In contrast, L. salivarius was internalized by THP-1 cells to a higher degree than B. fragilis or E. coli and was associated with a different cytokine profile. Microarray analysis showed both common and differential gene expression amongst the bacteria and control polystyrene beads. In the presence of bacteria, but not beads, upregulated genes were mainly involved in transcription regulation and dephosphorylation, e.g. EGR1, JUN; whereas proinflammatory and stress response genes were primarily upregulated by E. coli and B. fragilis, but not L. salivarius nor beads, e.g. IL8, TNFAIP3. These results demonstrate that M cells have the ability to discriminate between different commensal bacteria and modify subsequent immune responses. C2bbe1 cells were converted to M cells (C2M) following 21 days of culture on Transwells in the presence of Raji B cells. C2M cells were co-cultured alone, Lactobacillus salivarius, Eschericha coli, Bacteroides fragilis and control beads. Total RNA was extracted and processed for Affymetrix array hybridisation

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Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models

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