Academic Journal
Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects:Implications for Intestinal Pathologies
العنوان: | Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects:Implications for Intestinal Pathologies |
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المؤلفون: | van Gorp, Charlotte, de Lange, Ilse H., Hutten, Matthias C., Lopez-Iglesias, Carmen, Massy, Kimberly R. I., Kessels, Lilian, Knoops, Kevin, Cuijpers, Iris, Sthijns, Mireille M. J. P. E., Troost, Freddy J., van Gemert, Wim G., Spiller, Owen B., Birchenough, George M. H., Zimmermann, Luc J. I., Wolfs, Tim G. A. M. |
المصدر: | van Gorp , C , de Lange , I H , Hutten , M C , Lopez-Iglesias , C , Massy , K R I , Kessels , L , Knoops , K , Cuijpers , I , Sthijns , M M J P E , Troost , F J , van Gemert , W G , Spiller , O B , Birchenough , G M H , Zimmermann , L J I & Wolfs , T G A M 2024 , ' Antenatal Ureaplasma Infection Causes Colonic Mucus Barrier Defects : Implications for Intestinal Pathologies ' , International .... |
سنة النشر: | 2024 |
المجموعة: | Maastricht University Research Publications |
مصطلحات موضوعية: | Ureaplasma, perinatal inflammation, intestinal mucus barrier, goblet cell, necrotizing enterocolitis, colon, ENDOPLASMIC-RETICULUM STRESS, UNFOLDED PROTEIN RESPONSE, OXIDATIVE STRESS, GOBLET CELLS, RISK-FACTOR, ER STRESS, LAYERS, CHORIOAMNIONITIS, PERMEABILITY |
الوصف: | Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). Ureaplasma parvum (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier alterations, including those of the mucus barrier, remain under-investigated, despite their importance in NEC pathophysiology. Therefore, in this study, the hypothesis that antenatal UP exposure disturbs colonic mucus barrier integrity, thereby potentially contributing to NEC pathogenesis, was investigated. In an established ovine chorioamnionitis model, lambs were intra-amniotically exposed to UP or saline for 7 d from 122 to 129 d gestational age. Thereafter, colonic mucus layer thickness and functional integrity, underlying mechanisms, including endoplasmic reticulum (ER) stress and redox status, and cellular morphology by transmission electron microscopy were studied. The clinical significance of the experimental findings was verified by examining colon samples from NEC patients and controls. UP-exposed lambs have a thicker but dysfunctional colonic mucus layer in which bacteria-sized beads reach the intestinal epithelium, indicating undesired bacterial contact with the epithelium. This is paralleled by disturbed goblet cell MUC2 folding, pro-apoptotic ER stress and signs of mitochondrial dysfunction in the colonic epithelium. Importantly, the colonic epithelium from human NEC patients showed comparable mitochondrial aberrations, indicating that NEC-associated intestinal barrier injury already occurs during chorioamnionitis. This study underlines the pathogenic potential of UP during pregnancy; it demonstrates that antenatal UP infection leads to severe colonic mucus barrier deficits, providing a mechanistic link between antenatal infections and postnatal NEC development. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
Relation: | https://cris.maastrichtuniversity.nl/en/publications/a87c20b4-b22d-4044-8b0d-ef6f6b5ac925 |
DOI: | 10.3390/ijms25074000 |
الاتاحة: | https://cris.maastrichtuniversity.nl/en/publications/a87c20b4-b22d-4044-8b0d-ef6f6b5ac925 https://doi.org/10.3390/ijms25074000 |
Rights: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.8E023541 |
قاعدة البيانات: | BASE |
DOI: | 10.3390/ijms25074000 |
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