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Open AccessArticle

Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols

1
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
2
Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
3
Cardiff University School of Medicine, Cardiff CF10 3AT, Wales, UK
4
Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6202 AZ Maastricht, The Netherlands
5
Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff CF14 4XN, UK
6
MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK
7
Division of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
8
Division of Obstetrics and Gynecology, School of Medicine, The University of Western Australia, Crawley WA 6009, Australia
9
School of Women’s and Infant’s Health, The University of Western Australia, Crawley WA 6009, Australia
10
Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
11
Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2019, 11(5), 968; https://doi.org/10.3390/nu11050968
Received: 19 March 2019 / Revised: 23 April 2019 / Accepted: 25 April 2019 / Published: 27 April 2019
Chorioamnionitis, clinically most frequently associated with Ureaplasma, is linked to intestinal inflammation and subsequent gut injury. No treatment is available to prevent chorioamnionitis-driven adverse intestinal outcomes. Evidence is increasing that plant sterols possess immune-modulatory properties. Therefore, we investigated the potential therapeutic effects of plant sterols in lambs intra-amniotically (IA) exposed to Ureaplasma. Fetal lambs were IA exposed to Ureaplasma parvum (U. parvum, UP) for six days from 127 d–133 d of gestational age (GA). The plant sterols β-sitosterol and campesterol, dissolved with β-cyclodextrin (carrier), were given IA every two days from 122 d–131 d GA. Fetal circulatory cytokine levels, gut inflammation, intestinal injury, enterocyte maturation, and mucosal phospholipid and bile acid profiles were measured at 133 d GA (term 150 d). IA plant sterol administration blocked a fetal inflammatory response syndrome. Plant sterols reduced intestinal accumulation of proinflammatory phospholipids and tended to prevent mucosal myeloperoxidase-positive (MPO) cell influx, indicating an inhibition of gut inflammation. IA administration of plant sterols and carrier diminished intestinal mucosal damage, stimulated maturation of the immature epithelium, and partially prevented U. parvum-driven reduction of mucosal bile acids. In conclusion, we show that β-sitosterol and campesterol administration protected the fetus against adverse gut outcomes following UP-driven chorioamnionitis by preventing intestinal and systemic inflammation. View Full-Text
Keywords: chorioamnionitis; Ureaplasma parvum; ovine; plant sterols; β-sitosterol; campesterol; fetal inflammatory response syndrome; intestinal inflammation; intestinal lipidome chorioamnionitis; Ureaplasma parvum; ovine; plant sterols; β-sitosterol; campesterol; fetal inflammatory response syndrome; intestinal inflammation; intestinal lipidome
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van Gorp, C.; de Lange, I.H.; Spiller, O.B.; Dewez, F.; Cillero Pastor, B.; Heeren, R.M.A.; Kessels, L.; Kloosterboer, N.; van Gemert, W.G.; Beeton, M.L.; Stock, S.J.; Jobe, A.H.; Payne, M.S.; Kemp, M.W.; Zimmermann, L.J.; Kramer, B.W.; Plat, J.; Wolfs, T.G.A.M. Protection of the Ovine Fetal Gut against Ureaplasma-Induced Chorioamnionitis: A Potential Role for Plant Sterols. Nutrients 2019, 11, 968.

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