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Cited by 125Digestive system and related healthGastrointestinal motility and disordersCancer Cells and Metastasis

Human mini-guts: New insights into intestinal physiology and host–pathogen interactions

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In, Julie G., Foulke-Abel, Jennifer, Estes, Mary K., Zachos, Nicholas C., Kovbasnjuk, Olga, Donowitz, Mark·2016·Nature Reviews Gastroenterology & Hepatology
DOI 10.1038/nrgastro.2016.142PMC PMC5079760
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Abstract

The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5+ intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

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  • Immortalized colon cancer cell lines such as Caco-2, HT-29, and T84 contain vastly mutated genomes and altered transcriptional and metabolic profiles.

    “Until recently, human cell culture models for studying intestinal epithelial cell transport have generally used colon cancer cell lines such as Caco-2, HT-29, and T84 [38,39], which are immortalized and contain vastly mutated genomes in addition to altered transcriptional and metabolic profiles [40].”

    From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [40]

    The “Limitations of traditional intestinal models” section identifies Caco-2, HT29 and T84 as immortalized, cancer-derived cell lines and reports differences in protein expression from the human intestine. It does not say that their genomes are vastly mutated or that they have altered metabolic profiles; its protein-expression findings do not establish the broader claim about transcriptional profiles. (LLM, conf=0.86)

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Authors
In, J. G., Foulke-Abel, J., Estes, M. K., Zachos, N. C., Kovbasnjuk, O., & Donowitz, M.
Affiliations
  • Johns Hopkins University (US)
  • Baylor College of Medicine (US)
Corresponding author
Donowitz, Mark
ORCID
Venue
Nature Reviews Gastroenterology & Hepatology
Publisher
Springer Science and Business Media LLC
Published
2016-09-28
Volume
13
Issue
11
Pages
633-642
ISSN
  • 1759-5045 (ISSN-L)
  • 1759-5053
DOI
10.1038/nrgastro.2016.142
PMC
PMC5079760
OpenAlex
W2526238900
Cited by
125
References
11
Citations by year
2026: 2 · 2025: 12 · 2024: 6 · 2023: 6 · 2022: 17 · 2021: 20 · 2020: 17 · 2019: 12 · 2018: 15 · 2017: 17
FWCI
1.96
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Gastroenterology & Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UH3TR000504, UH3TR000503)
  • National Institute of Allergy and Infectious Diseases (R01AI080656, U19AI116497)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U24DK085532, T32DK007632, P30DK089502, K01DK106323, R01DK061765, R01DK026523, U01DK085532)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
colonoids, intestinal organoids, Lgr5+ intestinal stem cells, Wnt3a, host-pathogen interaction, gastrointestinal infections, intestinal epithelial differentiation, crypt-villus axis, in vitro intestinal model
MeSH terms
Biological Transport, Forecasting, Gastrointestinal Diseases, Humans, Infections, Intestine, Large, Intestine, Small, Models, Biological, Organoids, Host-Pathogen Interactions

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