Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier
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Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam(3)-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.
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- Authors
- Karczewski, J., Troost, F. J., Konings, I., Dekker, J., Kleerebezem, M., Brummer, R.-J. M., & Wells, J. M.
- Affiliations
- TiFN (NL)
- Maastricht University (NL)
- Örebro University (SE)
- Corresponding author
- Wells, Jerry M.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2010-06
- Volume
- 298
- Issue
- 6
- Pages
- G851-G859
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2101272036
- Cited by
- 676
- References
- 49
- Citations by year
- 2026: 36 · 2025: 43 · 2024: 50 · 2023: 43 · 2022: 62 · 2021: 67 · 2020: 56 · 2019: 45 · 2018: 35 · 2017: 41 · 2016: 33 · 2015: 30 · 2014: 39 · 2013: 32 · 2012: 28
- FWCI
- 47.11
- Type
- journal article
- Language
- en
- Open access
- green
- research.wur.nl
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Lactobacillus plantarum, tight junction proteins, intestinal barrier function, zonula occludens-1, occludin, TLR2, probiotics, commensal bacteria, epithelial permeability, phorbol ester, Caco-2 cells, intestinal homeostasis
- MeSH terms
- Adult, Duodenum, Epithelial Cells, Humans, Intestinal Mucosa, Membrane Proteins, Phosphoproteins, Signal Transduction, Cross-Over Studies, Microscopy, Confocal, Caco-2 Cells, Tight Junctions, Cytoprotection, Lactobacillus plantarum, Lactiplantibacillus plantarum, Toll-Like Receptor 2, Occludin, Zonula Occludens-1 Protein
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