{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:01:50Z","timestamp":1784588510750,"version":"3.55.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"\n The daily use of plastic products leads to exposure of populations via ingestion, which may affect intestinal health. While a wealth of studies has documented the impact of micro- and nanoplastics (MNPLs) on models representing healthy human intestine, less is known about their impact on sensitive populations, particularly those at risk of developing inflammatory bowel diseases. This study explored the intestinal response to carboxylated and aminated polystyrene particles (50\u2013500\u00a0nm PS-COOH and 50\u00a0nm\u00a0PS-NH\n 2<\/jats:sub>\n )\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n in models of genetic susceptibility to Crohn\u2019s disease. These models included nucleotide-binding oligomerization domain-2 wild-type and knock-out mice (Nod2\n \n WT<\/jats:italic>\n <\/jats:sup>\n and Nod2\n \n KO<\/jats:italic>\n <\/jats:sup>\n , respectively) and co-cultures of Caco-2 and HT29-MTX cells, with Caco2 cells stably expressing either wild-type NOD2 or the NOD2\n \n 1007fs<\/jats:italic>\n <\/jats:sup>\n variant, which is strongly associated with Crohn\u2019s disease.\n In vitro,<\/jats:italic>\n the co-cultures were used either in a non-differentiated state (\n i.e.<\/jats:italic>\n , 24\u00a0h post-seeding) or after differentiation into a tight, mucus-secreting epithelium. Results showed that\n in vivo<\/jats:italic>\n , single oral administration of PS-COOH particles impaired the paracellular permeability of the ileum of Nod2\n \n WT<\/jats:italic>\n <\/jats:sup>\n mice. Both PS-COOH and PS-NH\n 2<\/jats:sub>\n reduced the number of goblet cells in Nod2\n \n WT<\/jats:italic>\n <\/jats:sup>\n and Nod2\n \n KO<\/jats:italic>\n <\/jats:sup>\n mice as well as Muc4 secretion in Nod2\n \n WT<\/jats:italic>\n <\/jats:sup>\n mice, and PS-COOH reduced Muc4 secretion in Nod2\n \n KO<\/jats:italic>\n <\/jats:sup>\n mice. Single oral administration of PS-COOH or PS-NH\n 2<\/jats:sub>\n altered mRNA expression of genes involved in the production of antimicrobial peptide, inflammation, mucin secretion and endoplasmic reticulum stress pathways, in both Nod2\n \n WT<\/jats:italic>\n <\/jats:sup>\n and Nod2\n \n KO<\/jats:italic>\n <\/jats:sup>\n mice.\n In vitro,<\/jats:italic>\n PS-COOH showed no impact in Caco2-NOD2\n \n 1007fs<\/jats:italic>\n <\/jats:sup>\n \/HT29-MTX and in Caco2-NOD2\n \n WT<\/jats:italic>\n <\/jats:sup>\n \/HT29-MTX, whereas PS-NH\n 2<\/jats:sub>\n induced a similar toxic response in both cell systems. The intensity of this response depended on the cells\u2019 differentiation status and on the mode of exposure,\n i.e.,<\/jats:italic>\n acute versus repeated. Overall, this study explored, for the first time, the response of models of genetic susceptibility to Crohn\u2019s disease to exposure to PS-COOH and PS-NH\n 2<\/jats:sub>\n nanoplastics (NPLs). The obtained data provide new insight into how populations at risk of developing CD respond to PS-COOH and PS-NH\n 2<\/jats:sub>\n NPLs, i.e., new knowledge related to the impact of NPLs on this vulnerable population.\n <\/jats:p>","DOI":"10.3389\/ftox.2026.1839932","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T22:10:24Z","timestamp":1784585424000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal toxicity of functionalized polystyrene nanoplastics in NOD2 models of Crohn\u2019s disease susceptibility"],"prefix":"10.3389","volume":"8","author":[{"given":"Manon","family":"Dussol","sequence":"first","affiliation":[{"name":"Univ. Grenoble-Alpes, CEA, CNRS, Grenoble-INP, SyMMES-CIBEST","place":["Grenoble, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"M\u00e9nard","sequence":"additional","affiliation":[{"name":"IRSD, UMR 1220, INSERM, INRAE, Universit\u00e9 de Toulouse, ENVT","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaux","family":"Papin","sequence":"additional","affiliation":[{"name":"Univ. Grenoble-Alpes, CEA, CNRS, Grenoble-INP, SyMMES-CIBEST","place":["Grenoble, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeva","family":"Boul\u00e9e","sequence":"additional","affiliation":[{"name":"Univ. Grenoble-Alpes, CEA, CNRS, Grenoble-INP, SyMMES-CIBEST","place":["Grenoble, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9rane","family":"Bard","sequence":"additional","affiliation":[{"name":"Univ. 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