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

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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

DOI 10.1099/jmm.0.005801-0PMC PMC2887547

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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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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)
ORCID: Ohkusa, Toshifumi
Yoshida, Tsutomu
Watanabe, Sumio
Okayasu, Isao
Venue: Journal of Medical Microbiology
Publisher: Microbiology Society
Published: 2009-05-01
Volume: 58
Issue: 5
Pages: 535-545
ISSN: 0022-2615 (ISSN-L)
1473-5644
DOI: 10.1099/jmm.0.005801-0
PMC: PMC2887547
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: green
www.ncbi.nlm.nih.gov
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: Health Sciences › Medicine › Gastroenterology › 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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Commensal bacteria can enter colonic epithelial cells and induce proinflammatory cytokine secretion: a possible pathogenic mechanism of ulcerative colitis

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