Evidence map›Paper›PMID 26677983›Full record

ArticleGastroenterology2016

Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology.

Jennifer Foulke-Abel, Julie In, Jianyi Yin, Nicholas C Zachos, Olga Kovbasnjuk, Mary K Estes, Hugo de Jonge, Mark Donowitz

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
11.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 204 citations in OpenAlex.

  1. Flagellar regulation in enterotoxigenicInfection and immunity · 2026
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  9. The Use of Organoid Cultures in Advancing Nutrition Research.Advances in nutrition (Bethesda, Md.) · 2025
    Review
  10. Review
  11. Gastrointestinal tract, its pathophysiology andWorld journal of gastroenterology · 2025
    Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Live-Cell Calcium Imaging in 3D Intestinal Organoids.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review

75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Jennifer Foulke-AbelDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Julie InDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Jianyi YinDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Nicholas C ZachosDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Olga KovbasnjukDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Mary K EstesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
Hugo de JongeDepartment of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Mark DonowitzDepartment of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: mdonowit@jhmi.edu.
Johns Hopkins Medicine · USBaylor College of Medicine · USErasmus MC · NL

Funding

X-ray Crystallographic Studies on CalicivirusesP01AI057788 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI ATMAR, ROBERT L., ESTES, MARY KOLB · 2004 to 2024
$34.4M
Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Geoffrey A Preidis · 2001 to 2026
$28.3M
Novel Platforms for Human Intestinal Enteroids: Matrix, Mechanics, and TopographyU19AI116497 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI GRANDE-ALLEN, KATHRYN JANE · 2015 to 2025
$13.2M
Two-Photon Microscopy Imaging CoreP01DK072084 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2006 to 2013
$12.7M
Translational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0M
Translational Approaches to Develop Drug Therapy for DiarrheaR24DK099803 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2014 to 2019
$8.9M
Regulation of Rotavirus ReplicationR01AI080656 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI Sue Ellen Crawford, Mary Kolb Estes · 2009 to 2026
$7.9M
DIARRHEAL DISEASES: A PHYSIOLOGIC APPROACH TO TREATMENTR01DK026523 · NIDDK · TUFTS MEDICAL CENTER · PI DONOWITZ, MARK · 1986 to 2016
$7.8M
Measuring the Temporal-Spatial Responses of Dormancy and Drug Resistance in a Human Breast Cancer Metastatic Niche within a Liver-on-a-Chip Microphysiological PlatformUH3TR000503 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING · 2014 to 2016
$6.2M
Using iPSCs to model patient outcomes in nephrotic syndromeUH3TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2014 to 2016
$6.1M
BASIC SCIENCE RESEARCH IN DIGESTIVE DISEASEST32DK007632 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 1989 to 2018
$5.4M
PDZ Domain Proteins and NHE3 RegulationR01DK061765 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK, TSE, CHUNG-MING · 2004 to 2013
$4.7M
NCATS NIH HHS U18 TR000552NCATS NIH HHS U18-TR000552NCATS NIH HHS UH3 TR000503NCATS NIH HHS UH3-TR000503NCATS NIH HHS UH3 TR000504NCATS NIH HHS UH3-TR000504NIAID NIH HHS P01 AI057788NIAID NIH HHS R01 AI080656NIAID NIH HHS U19 AI116497NIDDK NIH HHS K01-DK088950NIDDK NIH HHS P01 DK072084NIDDK NIH HHS P01-DK072084NIDDK NIH HHS P30 DK056338NIDDK NIH HHS P30-DK056338NIDDK NIH HHS P30 DK089502NIDDK NIH HHS P30-DK089502NIDDK NIH HHS R01 DK026523NIDDK NIH HHS R01-DK026523NIDDK NIH HHS R01 DK061765NIDDK NIH HHS R01-DK061765NIDDK NIH HHS R24 DK099803NIDDK NIH HHS T32 DK007632NIDDK NIH HHS T32-DK007632
6 · The paper itself

Abstract

BACKGROUND &

aimsHuman intestinal crypt-derived enteroids are a model of intestinal ion transport that require validation by comparison with cell culture and animal models. We used human small intestinal enteroids to study neutral Na(+) absorption and stimulated fluid and anion secretion under basal and regulated conditions in undifferentiated and differentiated cultures to show their functional relevance to ion transport physiology and pathophysiology.

methodsHuman intestinal tissue specimens were obtained from an endoscopic biopsy or surgical resections performed at Johns Hopkins Hospital. Crypts were isolated, enteroids were propagated in culture, induced to undergo differentiation, and transduced with lentiviral vectors. Crypt markers, surface cell enzymes, and membrane ion transporters were characterized using quantitative reverse-transcription polymerase chain reaction, immunoblot, or immunofluorescence analyses. We used multiphoton and time-lapse confocal microscopy to monitor intracellular pH and luminal dilatation in enteroids under basal and regulated conditions.

resultsEnteroids differentiated upon withdrawal of WNT3A, yielding decreased crypt markers and increased villus-like characteristics. Na(+)/H(+) exchanger 3 activity was similar in undifferentiated and differentiated enteroids, and was affected by known inhibitors, second messengers, and bacterial enterotoxins. Forskolin-induced swelling was completely dependent on cystic fibrosis transmembrane conductance regulator and partially dependent on Na(+)/H(+) exchanger 3 and Na(+)/K(+)/2Cl(-) cotransporter 1 inhibition in undifferentiated and differentiated enteroids. Increases in cyclic adenosine monophosphate with forskolin caused enteroid intracellular acidification in HCO3(-)-free buffer. Cyclic adenosine monophosphate-induced enteroid intracellular pH acidification as part of duodenal HCO3(-) secretion appears to require cystic fibrosis transmembrane conductance regulator and electrogenic Na(+)/HCO3(-) cotransporter 1.

conclusionsUndifferentiated or crypt-like, and differentiated or villus-like, human enteroids represent distinct points along the crypt-villus axis; they can be used to characterize electrolyte transport processes along the vertical axis of the small intestine. The duodenal enteroid model showed that electrogenic Na(+)/HCO3(-) cotransporter 1 might be a target in the intestinal mucosa for treatment of secretory diarrheas.

Indexed as

Cell DifferentiationGene Expression RegulationHumansHydrogen-Ion ConcentrationIntestinal SecretionsIntestine, SmallIon TransportKineticsMembrane Transport ProteinsMicroscopy, ConfocalMicroscopy, Fluorescence, MultiphotonMicroscopy, VideoSodiumTime-Lapse ImagingTissue Culture TechniquesTransduction, GeneticMembrane Transport ProteinsSodiumIntestinal OrganoidsNa(+) AbsorptionNHE3 ActivityStimulated Secretion

Identifiers

PMID26677983
PMCPMC4766025
OpenAlexW2190931422

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.