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. 2023 Dec;15(2):2281012.
doi: 10.1080/19490976.2023.2281012. Epub 2023 Nov 22.

Detecting host responses to microbial stimulation using primary epithelial organoids

Jette Bornholdt  1   2   3 , Christina V Müller  1 , Maria Juul Nielsen  1 , Jesper Strickertsson  3 , Daria Rago  1   2 , Yun Chen  1   2   3 , Grzegorz Maciag  4 , Jonathan Skov  4 , Anja Wellejus  3 , Pawel J Schweiger  4 , Stine L Hansen  4 , Christa Broholm  3 , Ismail Gögenur  5   6 , Martti Maimets  4 , Stine Sloth  7 , Jakob Hendel  7 , Adam Baker  3 , Albin Sandelin  1   2 , Kim B Jensen  1   4
Affiliations

Detecting host responses to microbial stimulation using primary epithelial organoids

Jette Bornholdt et al. Gut Microbes. 2023 Dec.

Abstract

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.

Keywords: Intestinal organoids; bacterial–epithelial interactions; intestinal epithelium; microbiome; probiotics.

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Figures

Figure 1.
Figure 1.
Derivation of organoid lines from a cohort of healthy individuals.
Figure 2.
Figure 2.
Characterization of impact of media composition on organoid cultures.
Figure 3.
Figure 3.
Development and characterization of a 2D model for primary intestinal epithelial cells.
Figure 4.
Figure 4.
Response to coculture with different microbes.
Figure 5.
Figure 5.
Screening bacteria using 2D model for primary intestinal epithelial cells.
See this image and copyright information in PMC

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