Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies
Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). <i>Ureaplasma parvum</i> (UP) is clinically the most isolated microorganism in chorioamnionitis, but its pathogenicity remains debated. Chorioamnionitis is associated with ileal barrier changes, but colonic barrier al...
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MDPI AG
2024-04-01
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| author | Charlotte van Gorp Ilse H. de Lange Matthias C. Hütten Carmen López-Iglesias Kimberly R. I. Massy Lilian Kessels Kèvin Knoops Iris Cuijpers Mireille M. J. P. E. Sthijns Freddy J. Troost Wim G. van Gemert Owen B. Spiller George M. H. Birchenough Luc J. I. Zimmermann Tim G. A. M. Wolfs |
| author_facet | Charlotte van Gorp Ilse H. de Lange Matthias C. Hütten Carmen López-Iglesias Kimberly R. I. Massy Lilian Kessels Kèvin Knoops Iris Cuijpers Mireille M. J. P. E. Sthijns Freddy J. Troost Wim G. van Gemert Owen B. Spiller George M. H. Birchenough Luc J. I. Zimmermann Tim G. A. M. Wolfs |
| author_sort | Charlotte van Gorp |
| collection | DOAJ |
| description | Chorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). <i>Ureaplasma parvum</i> (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. |
| first_indexed | 2024-04-24T10:42:03Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-04-24T10:42:03Z |
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| spelling | doaj.art-2d807d7de6374cccad5d29a4061831072024-04-12T13:20:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257400010.3390/ijms25074000Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal PathologiesCharlotte van Gorp0Ilse H. de Lange1Matthias C. Hütten2Carmen López-Iglesias3Kimberly R. I. Massy4Lilian Kessels5Kèvin Knoops6Iris Cuijpers7Mireille M. J. P. E. Sthijns8Freddy J. Troost9Wim G. van Gemert10Owen B. Spiller11George M. H. Birchenough12Luc J. I. Zimmermann13Tim G. A. M. Wolfs14Department of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Pediatrics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6211 LK Maastricht, The NetherlandsDepartment of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsMicroscopy CORE Lab, Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6211 LK Maastricht, The NetherlandsFood Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The NetherlandsFood Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The NetherlandsFood Innovation and Health, Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 5911 BV Venlo, The NetherlandsDepartment of Surgery, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6229 ER Maastricht, The NetherlandsDivision of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XW, UKDepartment of Medical Biochemistry, Institute of Biomedicine, University of Gothenburg, 40530 Gothenburg, SwedenDepartment of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Pediatrics, School for Oncology and Reproduction (GROW), Maastricht University, 6229 ER Maastricht, The NetherlandsChorioamnionitis is a risk factor for necrotizing enterocolitis (NEC). <i>Ureaplasma parvum</i> (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.https://www.mdpi.com/1422-0067/25/7/4000<i>Ureaplasma</i>perinatal inflammationintestinal mucus barriergoblet cellnecrotizing enterocolitiscolon |
| spellingShingle | Charlotte van Gorp Ilse H. de Lange Matthias C. Hütten Carmen López-Iglesias Kimberly R. I. Massy Lilian Kessels Kèvin Knoops Iris Cuijpers Mireille M. J. P. E. Sthijns Freddy J. Troost Wim G. van Gemert Owen B. Spiller George M. H. Birchenough Luc J. I. Zimmermann Tim G. A. M. Wolfs Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies International Journal of Molecular Sciences <i>Ureaplasma</i> perinatal inflammation intestinal mucus barrier goblet cell necrotizing enterocolitis colon |
| title | Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies |
| title_full | Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies |
| title_fullStr | Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies |
| title_full_unstemmed | Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies |
| title_short | Antenatal <i>Ureaplasma</i> Infection Causes Colonic Mucus Barrier Defects: Implications for Intestinal Pathologies |
| title_sort | antenatal i ureaplasma i infection causes colonic mucus barrier defects implications for intestinal pathologies |
| topic | <i>Ureaplasma</i> perinatal inflammation intestinal mucus barrier goblet cell necrotizing enterocolitis colon |
| url | https://www.mdpi.com/1422-0067/25/7/4000 |
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