Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function
Abstract
Live probiotic bacteria are effective in reducing gut permeability and inflammation. We have previously shown that probiotics release peptide bioactive factors that modulate epithelial resistance in vitro. The objectives of this study were to determine the impact of factors released from Bifidobacteria infantis on intestinal epithelial cell permeability and tight junction proteins and to assess whether these factors retain their bioactivity when administered to IL-10-deficient mice. B. infantis conditioned medium (BiCM) was applied to T84 human epithelial cells in the presence and absence of TNF-alpha and IFN-gamma. Transepithelial resistance (TER), tight junction proteins [claudins 1, 2, 3, and 4, zonula occludens (ZO)-1, and occludin] and MAP kinase activity (p38 and ERK) were examined. Acute effects of BiCM on intestinal permeability were assessed in colons from IL-10-deficient mice in Ussing chambers. A separate group of IL-1-deficient mice was treated with BiCM for 4 wk and then assessed for intestinal histological injury, cytokine levels, epithelial permeability, and immune response to bacterial antigens. In T84 cells, BiCM increased TER, decreased claudin-2, and increased ZO-1 and occludin expression. This was associated with enhanced levels of phospho-ERK and decreased levels of phospho-p38. BiCM prevented TNF-alpha- and IFN-gamma-induced drops in TER and rearrangement of tight junction proteins. Inhibition of ERK prevented the BiCM-induced increase in TER and attenuated the protection from TNF-alpha and IFN-gamma. Oral BiCM administration acutely reduced colonic permeability in mice whereas long-term BiCM treatment in IL-10-deficient mice attenuated inflammation, normalized colonic permeability, and decreased colonic and splenic IFN-gamma secretion. In conclusion, peptide bioactive factors from B. infantis retain their biological activity in vivo and are effective in normalizing gut permeability and improving disease in an animal model of colitis. The effects of BiCM are mediated in part by changes in MAP kinases and tight junction proteins.
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Probiotics such as Lactobacillus, Bifidobacterium, and Ackermannia may enhance intestinal integrity through various mechanisms, normalizing intestinal cytokine levels, balancing intestinal immunity, and reducing inflammation.
“Probiotics such as Lactobacillus, Bifidobacterium, and Ackermannia may enhance intestinal integrity through a variety of mechanisms [21–24], normalizing intestinal cytokine levels, balancing intestinal immunity, and reducing inflammation.”
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- Authors
- Ewaschuk, J. B., Diaz, H., Meddings, L., Diederichs, B., Dmytrash, A., Backer, J., Looijer-van Langen, M., & Madsen, K. L.
- Affiliations
- University of Alberta (CA)
- ORCID
- Madsen, Karen L.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2008-11
- Volume
- 295
- Issue
- 5
- Pages
- G1025-G1034
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W2141878383
- Cited by
- 590
- References
- 50
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 24 · 2023: 51 · 2022: 34 · 2021: 45 · 2020: 34 · 2019: 25 · 2018: 37 · 2017: 43 · 2016: 42 · 2015: 39 · 2014: 33 · 2013: 37 · 2012: 27
- FWCI
- 41.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Bifidobacterium infantis, intestinal epithelial barrier function, intestinal permeability, tight junction proteins, claudin-2, ZO-1, occludin, MAPK signaling, ERK, p38 MAPK, TNF-α, interferon-gamma, IL-10-deficient mice, colitis, colonic inflammation, oral administration
- MeSH terms
- Animals, Bifidobacterium, Gene Expression Regulation, Humans, Intestines, Membrane Proteins, Phosphorylation, Interleukin-10, Culture Media, Conditioned, Gene Deletion, Probiotics, Mitogen-Activated Protein Kinase Kinases, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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