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They parasitize the apical surface of the epithelial cells in the intestinal lumen. However, the pathogenesis of <jats:italic>Cryptosporidium<\/jats:italic>-induced diarrhea is not fully understood yet.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/principal findings<\/jats:title>\n<jats:p>In this study, we infected C57BL\/6j neonatal mice with <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IIa and IId subtypes, and examined oocyst burden, pathological changes, and intestinal epithelial permeability during the infection. In addition, transcriptomic analyses were used to study the mechanism of diarrhea induced by the <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IId subtype. The neonatal mice were sensitive to both <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IIa and IId infection, but the IId subtype caused a wide oocyst shedding window and maintained the high oocyst burden in the mice compared with the IIa subtype. In addition, the mice infected with <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IId resulted in severe intestinal damage at the peak of infection, leading to increased permeability of the epithelial barrier. The KEGG, GO and GSEA analyses revealed that the downregulation of adherens junction and cell junction molecules at 11 dpi. Meanwhile, E-cadherin, which is associated with adherens junction, was reduced at the protein level in mouse ileum at peak and late infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/significance<\/jats:title>\n<jats:p><jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IId infection causes more severe pathological damage than <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IIa infection in neonatal mice. Furthermore, the impairment of the epithelial barrier during <jats:italic>C<\/jats:italic>. <jats:italic>parvum<\/jats:italic> IId infection results from the downregulation of intestinal junction proteins.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012212","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T17:41:38Z","timestamp":1716572498000},"page":"e0012212","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cryptosporidium parvum disrupts intestinal epithelial barrier in neonatal mice through downregulation of cell junction 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