Cited by 167Inflammatory Bowel DiseaseGut microbiota and healthProbiotics and Fermented Foods

Commensal Bacteria Can Enter Colonic Epithelial Cells and Induce Proinflammatory Cytokine Secretion: A Possible Pathogenic Mechanism of Ulcerative Colitis

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Ohkusa, Toshifumi, Yoshida, Tsutomu, Sato, Nobuhiro, Watanabe, Sumio, Tajiri, Hisao, Okayasu, Isao·2009·Journal of Medical Microbiology

Abstract

Interleukin 2 (IL-2)- and IL-10-knockout mice develop spontaneous colitis under conventional but not germ-free conditions, suggesting that commensal bacteria play an important role in the pathogenesis of colitis. However, interactions between commensal bacteria and colonic epithelial cells have not been fully investigated. We therefore assessed the ability of various commensal bacteria and probiotics to adhere to and invade colonic epithelial cells. Effects of the bacteria on production of proinflammatory cytokines were also measured. Commensal bacteria, including mucosal organisms isolated from ulcerative colitis (UC) patients, such as Fusobacterium varium, reported as a possible pathogen in UC, Bacteroides vulgatus, Escherichia coli and Clostridium clostridioforme, as well as their type strains and probiotics, were assessed for their ability to adhere to and invade colonic epithelial cells using two cell lines, SW-480 and HT-29. Our experiments employed co-incubation, a combination of scanning and transmission electron microscopy and recovery of bacteria from infected-cell lysates. F. varium and several other commensal bacteria, but not probiotics, adhered to colonic epithelial cells and invaded their cytoplasm. ELISA and real-time PCR revealed that the host cells, particularly those invaded by F. varium, showed significant increases in IL-8 and TNF-alpha concentrations in supernatants, with elevation of IL-8, TNF-alpha, MCP-1 and IL-6 mRNAs. Furthermore, IL-8 and TNF-alpha expression and nuclear phosphorylated NF-kappaB p65 expression could be immunohistochemically confirmed in inflamed epithelium with cryptitis or crypt abscess in UC patients. Certain commensal bacteria can invade colonic epithelial cells, activating early intracellular signalling systems to trigger host inflammatory reactions.

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Crossref · 10.1099/jmm.0.005801-0

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Authors
Ohkusa, T., Yoshida, T., Sato, N., Watanabe, S., Tajiri, H., & Okayasu, I.
Affiliations
  • Jikei University School of Medicine (JP)
  • Kitasato University (JP)
  • Juntendo University (JP)
Venue
Journal of Medical Microbiology
Published
2009-05-01
Volume
58
Issue
5
Pages
535-545
ISSN
  • 0022-2615 (ISSN-L)
  • 1473-5644
OpenAlex
W2155286505
Cited by
167
References
38
Citations by year
2026: 12 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 17 · 2021: 15 · 2020: 14 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 14 · 2013: 5 · 2012: 5
FWCI
3.49
Type
journal article
Language
en
Open access
Locations
  • Journal of Medical Microbiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Uehara Memorial Foundation
  • Ministry of Education, Culture, Sports, Science and Technology
  • National Institutes of Health (5r01de008293-15, 5p50de008240-10)
  • National Institute of General Medical Sciences (GM54666, R01GM054666)
  • National Institute of Allergy and Infectious Diseases (AI 09268, F32AI009268)
  • National Institute of Dental and Craniofacial Research (DE08293, DE08240)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
commensal bacteria, ulcerative colitis, colonic epithelial cells, bacterial invasion, bacterial adhesion, inflammatory cytokines, Fusobacterium varium, Bacteroides vulgatus, Escherichia coli, Clostridium clostridioforme, probiotics, interleukin-8, TNF-α, NF-κB p65, cryptitis, crypt abscesses, intestinal inflammation
MeSH terms
Adenocarcinoma, Animals, Bacterial Adhesion, Colitis, Ulcerative, Colon, Colonic Neoplasms, Humans, Inflammation, Interleukin-2, Intestinal Mucosa, Cytokines, Interleukin-8, Interleukin-10, DNA Primers, Mice, Knockout, Cell Line, Tumor, Mice

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