Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis: A potential role for plant sterols

Charlotte van Gorp, Ilse H. de Lange, Owen B. Spiller, Frédéric Dewez, Berta Cillero Pastor, Ron M.A. Heeren, Lilian Kessels, Nico Kloosterboer, Wim G. van Gemert, Michael L. Beeton, Sarah J. Stock, Alan H. Jobe, Matthew S. Payne, Matthew W. Kemp, Luc J. Zimmermann, Boris W. Kramer, Jogchum Plat, Tim G.A.M. Wolfs

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number968
JournalNutrients
Volume11
Issue number5
DOIs
Publication statusPublished - 1 May 2019

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Ureaplasma
Chorioamnionitis
Phytosterols
Ureaplasma parvum
phytosterols
Sheep
digestive system
sheep
inflammation
gestational age
Gestational Age
Inflammation
campesterol
sitosterols
bile acids
Bile Acids and Salts
Phospholipids
phospholipids
lambs
myeloperoxidase

Cite this

van Gorp, C., de Lange, I. H., Spiller, O. B., Dewez, F., Pastor, B. C., Heeren, R. M. A., ... Wolfs, T. G. A. M. (2019). Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis: A potential role for plant sterols. Nutrients, 11(5), [968]. https://doi.org/10.3390/nu11050968
van Gorp, Charlotte ; de Lange, Ilse H. ; Spiller, Owen B. ; Dewez, Frédéric ; Pastor, Berta Cillero ; Heeren, Ron M.A. ; Kessels, Lilian ; Kloosterboer, Nico ; van Gemert, Wim G. ; Beeton, Michael L. ; Stock, Sarah J. ; Jobe, Alan H. ; Payne, Matthew S. ; Kemp, Matthew W. ; Zimmermann, Luc J. ; Kramer, Boris W. ; Plat, Jogchum ; Wolfs, Tim G.A.M. / Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis : A potential role for plant sterols. In: Nutrients. 2019 ; Vol. 11, No. 5.
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abstract = "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.",
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van Gorp, C, de Lange, IH, Spiller, OB, Dewez, F, Pastor, BC, Heeren, RMA, Kessels, L, Kloosterboer, N, van Gemert, WG, Beeton, ML, Stock, SJ, Jobe, AH, Payne, MS, Kemp, MW, Zimmermann, LJ, Kramer, BW, Plat, J & Wolfs, TGAM 2019, 'Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis: A potential role for plant sterols' Nutrients, vol. 11, no. 5, 968. https://doi.org/10.3390/nu11050968

Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis : A potential role for plant sterols. / van Gorp, Charlotte; de Lange, Ilse H.; Spiller, Owen B.; Dewez, Frédéric; Pastor, Berta Cillero; Heeren, Ron M.A.; Kessels, Lilian; Kloosterboer, Nico; van Gemert, Wim G.; Beeton, Michael L.; Stock, Sarah J.; Jobe, Alan H.; Payne, Matthew S.; Kemp, Matthew W.; Zimmermann, Luc J.; Kramer, Boris W.; Plat, Jogchum; Wolfs, Tim G.A.M.

In: Nutrients, Vol. 11, No. 5, 968, 01.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis

T2 - A potential role for plant sterols

AU - van Gorp, Charlotte

AU - de Lange, Ilse H.

AU - Spiller, Owen B.

AU - Dewez, Frédéric

AU - Pastor, Berta Cillero

AU - Heeren, Ron M.A.

AU - Kessels, Lilian

AU - Kloosterboer, Nico

AU - van Gemert, Wim G.

AU - Beeton, Michael L.

AU - Stock, Sarah J.

AU - Jobe, Alan H.

AU - Payne, Matthew S.

AU - Kemp, Matthew W.

AU - Zimmermann, Luc J.

AU - Kramer, Boris W.

AU - Plat, Jogchum

AU - Wolfs, Tim G.A.M.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Campesterol

KW - Chorioamnionitis

KW - Fetal inflammatory response syndrome

KW - Intestinal inflammation

KW - Intestinal lipidome

KW - Ovine

KW - Plant sterols

KW - Ureaplasma parvum

KW - β-sitosterol

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U2 - 10.3390/nu11050968

DO - 10.3390/nu11050968

M3 - Article

VL - 11

JO - Nutrients

JF - Nutrients

SN - 2072-6643

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M1 - 968

ER -