Detecting host responses to microbial stimulation using primary epithelial organoids.

Autor: Bornholdt J; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; Department of Biology, University of Copenhagen, Copenhagen, Denmark.; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Müller CV; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark., Nielsen MJ; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark., Strickertsson J; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Rago D; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; Department of Biology, University of Copenhagen, Copenhagen, Denmark., Chen Y; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; Department of Biology, University of Copenhagen, Copenhagen, Denmark.; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Maciag G; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark., Skov J; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark., Wellejus A; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Schweiger PJ; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark., Hansen SL; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark., Broholm C; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Gögenur I; Center for Surgical Science, Department of Surgery, Zealand University Hospital, Koge, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Maimets M; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark., Sloth S; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark., Hendel J; Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark., Baker A; Human Health Research, Chr. Hansen AS, Hørsholm, Denmark., Sandelin A; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; Department of Biology, University of Copenhagen, Copenhagen, Denmark., Jensen KB; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Gut microbes [Gut Microbes] 2023 Dec; Vol. 15 (2), pp. 2281012. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1080/19490976.2023.2281012
Abstrakt: The intestinal epithelium is constantly exposed to microbes residing in the lumen. Traditionally, the response to microbial interactions has been studied in cell lines derived from cancerous tissues, e.g. Caco-2. It is, however, unclear how the responses in these cancer cell lines reflect the responses of a normal epithelium and whether there might be microbial strain-specific effects. To address these questions, we derived organoids from the small intestine from a cohort of healthy individuals. Culturing intestinal epithelium on a flat laminin matrix induced their differentiation, facilitating analysis of microbial responses via the apical membrane normally exposed to the luminal content. Here, it was evident that the healthy epithelium across multiple individuals ( n  = 9) demonstrates robust acute both common and strain-specific responses to a range of probiotic bacterial strains (BB-12 Ⓡ , LGG Ⓡ , DSM33361, and Bif195). Importantly, parallel experiments using the Caco-2 cell line provide no acute response. Collectively, we demonstrate that primary epithelial cells maintained as organoids represent a valuable resource for assessing interactions between the epithelium and luminal microbes across individuals, and that these models are likely to contribute to a better understanding of host microbe interactions.
Databáze: MEDLINE
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