Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology

van Gorp, Charlotte, de Lange, Ilse H, Hütten, Matthias C, López-Iglesias, Carmen, Massy, Kimberly RI, Kessels, Lilian, Kramer, Boris, van de Wetering, Willine, Spiller, Brad ORCID: https://orcid.org/0000-0002-9117-6911, Birchenough, George M, van Gemert, Wim G, Zimmermann, Luc J and Wolfs, Tim GAM 2022. Antenatal Ureaplasma infection induces ovine small intestinal goblet cell defects: a strong link with NEC pathology. Tissue Barriers , 2158016. 10.1080/21688370.2022.2158016

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Abstract

Disruption of the intestinal mucus barrier and intestinal epithelial endoplasmic reticulum (ER) stress contribute to necrotizing enterocolitis (NEC). Previously, we observed intestinal goblet cell loss and increased intestinal epithelial ER stress following chorioamnionitis. Here, we investigated how chorioamnionitis affects goblet cells by assessing their cellular characteristics. Importantly, goblet cell features are compared with those in clinical NEC biopsies. Mucus thickness was assessed as read-out of goblet cell function. Fetal lambs were intra-amniotically (IA) infected for 7d at 122 gestational age with Ureaplasma parvum serovar-3, the main microorganism clinically associated with chorioamnionitis. After preterm delivery, mucus thickness, goblet cell numbers, gut inflammation, epithelial proliferation and apoptosis and intestinal epithelial ER stress were investigated in the terminal ileum. Next, goblet cell morphological alterations (TEM) were studied and compared to human NEC samples. Ileal mucus thickness and goblet cell numbers were elevated following IA UP exposure. Increased pro-apoptotic ER stress, detected by elevated CHOP-positive cell counts and disrupted organelle morphology of secretory cells in the intestinal epithelium, was observed in IA UP exposed animals. Importantly, comparable cellular morphological alterations were observed in the ileum from NEC patients. In conclusion, UP-driven chorioamnionitis leads to a thickened ileal mucus layer and mucus hypersecretion from goblet cells. Since this was associated with pro-apoptotic ER stress and organelle disruption, mucus barrier alterations seem to occur at the expense of goblet cell resilience and may therefore predispose to detrimental intestinal outcomes. The remarkable overlap of these in utero findings with observations in NEC patients underscores their clinical relevance.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Taylor and Francis Group
ISSN:	2168-8370
Date of First Compliant Deposit:	10 February 2023
Date of Acceptance:	5 December 2022
Last Modified:	02 May 2023 17:49
URI:	https://orca.cardiff.ac.uk/id/eprint/156888

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