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Human exposure to foodborne inorganic nanoparticles (NPs) is a growing concern. However, identifying potential hazards linked to NP ingestion often requires long-term exposure in animals. Owing these constraints, intestinal organoids are a promising alternative to in vivo experiments; as such, an in vitro approach should enable a rapid and reliable assessment of the effects of ingested chemicals on the gut. However, this remains to be validated for inorganic substances. In our study, a transcriptomic analysis and immunofluorescence staining were performed to compare the effects of food-grade TiO (-TiO) on enteroid-derived monolayers (EDMs) from murine intestinal organoids to the known impacts of TiO on intestinal epithelium. After their ability to respond to a pro-inflammatory cytokine cocktail was validated, EDMs were exposed to 0, 0.1, 1, or 10 µg -TiO/mL for 24 h. A dose-related increase of the , , and gene markers of cell differentiation was observed. In addition, -TiO induced apoptosis and dose-dependent genotoxicity, while a decreased expression of genes encoding for antimicrobial peptides, and of genes related to tight junction function, was observed. These results validated the use of EDMs as a reliable model for the toxicity testing of foodborne NPs likely to affect the intestinal barrier.
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http://dx.doi.org/10.3390/ijms25052635 | DOI Listing |
Bioengineering (Basel)
July 2025
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA.
Accurate in vitro models of intestinal permeability are essential for predicting oral drug absorption. Standard models like Caco-2 cells have well-known limitations, including lack of segment-specific physiology, but are widely used. Emerging models such as organoid-derived monolayers and microphysiological systems (MPS) offer enhanced physiological relevance but require comparative validation.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
May 2025
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Paratuberculosis is an infectious disease caused by the bacterium, subspecies (MAP). MAP infection of ruminants triggers progressive wasting disease characterized by granulomatous lymphadenitis, enteritis, and severe intestinal pathology that often requires early culling of the animal. The resulting economic burden is significant, and MAP exposure in the workplace constitutes a significant zoonotic risk.
View Article and Find Full Text PDFToxicol Sci
April 2025
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, United States.
Intestinal absorption is a key toxicokinetics parameter. Although the colon carcinoma cell line Caco-2 is the most used in vitro model to estimate human drug absorption, models representing other intestinal segments are available. We characterized the morphology, tissue-specific markers, and functionality of 3 human intestinal cell types: Caco-2, primary human enteroid-derived cells from jejunum (J2), and duodenum (D109) when cultured in the OrganoPlate 3-lane 40 microphysiological system (MPS) or static 24-well Transwells.
View Article and Find Full Text PDFJ Vis Exp
April 2024
Department of Farm Animal Medicine, College of Veterinary Medicine, Midwestern University;
Organoid cell culture systems can recapitulate the complexity observed in tissues, making them useful in studying host-pathogen interactions, evaluating drug efficacy and toxicity, and tissue bioengineering. However, applying these models for the described reasons may be limited because of the three-dimensional (3D) nature of these models. For example, using 3D enteroid culture systems to study digestive diseases is challenging due to the inaccessibility of the intestinal lumen and its secreted substances.
View Article and Find Full Text PDFInt J Mol Sci
February 2024
Toxalim UMR1331 (Research Centre in Food Toxicology), Toulouse University, INRAE, ENVT, INP-Purpan, UPS, 31027 Toulouse, France.