Digestive Diseases and Sciences

, Volume 64, Issue 2, pp 409–420 | Cite as

Homoectoine Protects Against Colitis by Preventing a Claudin Switch in Epithelial Tight Junctions

  • Karla F. Castro-Ochoa
  • Hilda Vargas-Robles
  • Sandra Chánez-Paredes
  • Alfonso Felipe-López
  • Rodolfo I. Cabrera-Silva
  • Mineko Shibayama
  • Abigail Betanzos
  • Porfirio Nava
  • Erwin A. Galinski
  • Michael SchnoorEmail author
Original Article



Inflammatory bowel diseases (IBD) are multifactorial disorders affecting millions of people worldwide with alarmingly increasing incidences every year. Dysfunction of the intestinal epithelial barrier is associated with IBD pathogenesis, and therapies include anti-inflammatory drugs that enhance intestinal barrier function. However, these drugs often have adverse side effects thus warranting the search for alternatives. Compatible solutes such as bacterial ectoines stabilize cell membranes and proteins.


To unravel whether ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and homoectoine (4,5,6,7-tetrahydro-2-methyl-1H-(1,3)-diazepine-4-carboxylic acid), a synthetic derivative of ectoine, have beneficial effects during dextran sulfate sodium (DSS)-induced colitis in mice.


We found that the disease activity index was significantly reduced by both ectoines. DSS-induced edema formation, epithelial permeability, leukocyte recruitment and tissue damage were reduced by ectoine and homoectoine, with the latter having stronger effects. Interestingly, the claudin switch usually observed during colitis (decreased expression of claudin-1 and increased expression of the leaky claudin-2) was completely prevented by homoectoine, whereas ectoine only reduced claudin-2 expression. Concomitantly, only homoectoine ameliorated the drop in transepithelial electrical resistance induced by IFN-γ and TNF-α in Caco-2 cells. Both ectoines inhibited loss of ZO-1 and occludin and prevented IFN-γ/TNF-α-induced increased paracellular flux of 4 kDa FITC-dextran in vitro. Moreover, both ectoines reduced expression of pro-inflammatory cytokines and oxidative stress during colitis.


While both ectoine and homoectoine have protective effects on the epithelial barrier during inflammation, only homoectoine completely prevented the inflammatory claudin switch in tight junctions. Thus, homoectoine may serve as diet supplement in IBD patients to reach or extend remission.


Ectoine Intestinal permeability Tight junction Pro-inflammatory cytokines Dextran sulfate sodium 



Adherens junction


Apical junction complex


Crohn’s disease


Disease activity index


Dextran sulfate sodium


Inflammatory bowel diseases










Reactive oxygen species


Transepithelial electrical resistance


Tight junction


2,4,6-Trinitrobenzenesulfonic acid


Tumor necrosis factor alpha


Ulcerative colitis


Zonula occludens



We thank Angélica Silva Olivares for expert technical assistance.


This work was supported by grants of the Mexican Council for Science and Technology (CONACyT, 233395 and 207268 to MS).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Karla F. Castro-Ochoa
    • 1
  • Hilda Vargas-Robles
    • 1
  • Sandra Chánez-Paredes
    • 1
  • Alfonso Felipe-López
    • 1
    • 6
  • Rodolfo I. Cabrera-Silva
    • 1
  • Mineko Shibayama
    • 2
  • Abigail Betanzos
    • 2
    • 3
  • Porfirio Nava
    • 4
  • Erwin A. Galinski
    • 5
  • Michael Schnoor
    • 1
    Email author
  1. 1.Department of Molecular BiomedicineCINVESTAVMexico-CityMexico
  2. 2.Department of Infectomics and Molecular PathogenesisCINVESTAVMexico-CityMexico
  3. 3.ConacytMexico-CityMexico
  4. 4.Department of Physiology, Biophysics and NeurosciencesCINVESTAVMexico-CityMexico
  5. 5.Institute of Microbiology and BiotechnologyUniversity of BonnBonnGermany
  6. 6.Molecular Biology Division, Navy Medical CenterMinistry of Marine and ArmyMexico-CityMexico

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