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Modeling host-microbe interactions in immunocompetent engineered human gut tissues

Lopez-Sandoval, R.; Harter, M. F.; Yu, Q.; Gaspa-Toneu, L.; Cubela, I.; Kromer, K.; Aubert, J.; Filip, A. M.; Kaltenbach, L.; Almato-Bellavista, M.; Akkerman, N.; Bollen, Y.; Munteanu, S.; Fidelin, J.; Augustin, A.; Schori, C.; Bickle, M.; Lutolf, M. P.; Beumer, J.; Recaldin, T.; Nikolaev, M.; Gjorevski, N.; Camp, J. G.

2025-05-07 bioengineering
10.1101/2025.05.02.651468 bioRxiv
Show abstract

The intestinal mucosal barrier contains microbial organisms within the lumen while preserving the ability to absorb nutrients. Dietary, microbial, and other exposures shaped human barrier evolution and continue to impact disease susceptibility. Here, we established engineered barrier models of the human small intestine and colon composed of a multilineage epithelium, mucus layer, accessible microbial compartment and autologous tissue-resident immune cells. The epithelium has crypt- and villus-like topological domains, with stem cells differentiating into absorptive and secretory lineages with region-specific identities. Secreted mucins accumulate apically, forming a dense mucus layer separating the epithelium from colonizing commensal and pathogenic bacteria. Intestinal memory T cells integrate into and interact with the epithelium. We use the engineered intestinal tissues to identify an epithelial gene regulatory network underlying response to Salmonella Typhimurium infection, and uncover epithelial-immune-pathogen crosstalk coordinating cytokine release and epithelial damage. Overall, this work allows for the modular integration of epithelial, microbial, and immune compartments providing a versatile system for studying human intestinal physiology and pathologies.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.