Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism
Open accessAbstract
BACKGROUND: We previously showed that the probiotic mixture, VSL#3, prevents the onset of ileitis in SAMP/YitFc (SAMP) mice, and this effect was associated with stimulation of epithelial-derived TNF. The aim of this study was to determine the mechanism(s) of VSL#3-mediated protection on epithelial barrier function and to further investigate the "paradoxical" effects of TNF in preventing SAMP ileitis. METHODS: Permeability was evaluated in SAMP mice prior to the onset of inflammation and during established disease by measuring transepithelial electrical resistance (TEER) on ex vivo-cultured ilea following exposure to VSL#3 conditioned media (CM), TNF or VSL#3-CM + anti-TNF. Tight junction (TJ) proteins were assessed by qRT-PCR, Western blot, and confocal microscopy, and TNFRI/TNFRII expression measured in freshly isolated intestinal epithelial cells (IEC) from SAMP and control AKR mice. RESULTS: Culture with either VSL#3-CM or TNF resulted in decreased ileal paracellular permeability in pre-inflamed SAMP, but not SAMP with established disease, while addition of anti-TNF abrogated these effects. Modulation of the TJ proteins, claudin-2 and occludin, occurred with a significant decrease in claudin-2 and increase in occludin following stimulation with VSL#3-CM or TNF. TNF protein levels increased in supernatants of SAMP ilea incubated with VSL#3-CM compared to vehicle, while IEC-derived TNFR mRNA expression decreased in young, and was elevated in inflamed, SAMP versus AKR mice. CONCLUSIONS: Our data demonstrate that the previously established efficacy of VSL#3 in preventing SAMP ileitis is due to direct innate and homeostatic effects of TNF on the gut epithelium, modulation of the TJ proteins, claudin-2 and occludin, and overall improvement of intestinal permeability.
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Various studies have reported beneficial effects of probiotics by enhancing intestinal epithelial integrity, protecting from barrier disruption, stimulating a healthy homeostasis of the mucosal immune system and suppressing pathogenic bacterial growth.
“Various studies have reported the beneficial effects of probiotics by enhancing intestinal epithelial integrity, protecting from barrier disruption, stimulating a healthy homeostasis of the mucosal immune system and suppressing pathogenic bacterial growth (Ait-Belgnaoui et al., 2012;Corridoni et al., 2012;Patel et al., 2012;Sartor, 2005;Zareie et al., 2006).”
From The Gut-Brain Axis in Parkinson’s Disease: Possibilities for Food-Based Therapies (2017) · cites this paper as Corridoni et al., 2012
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- Authors
- Corridoni, D., Pastorelli, L., Mattioli, B., Locovei, S., Ishikawa, D., Arseneau, K. O., Chieppa, M., Cominelli, F., & Pizarro, T. T.
- Affiliations
- Case Western Reserve University (US)
- Gastroenterology Hospital "Saverio de Bellis" (IT)
- Corresponding author
- Pizarro, Theresa T.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-07-25
- Volume
- 7
- Issue
- 7
- Pages
- e42067
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3405026
- OpenAlex
- W2035314723
- Cited by
- 118
- References
- 62
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 14 · 2021: 9 · 2020: 12 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 1
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- AIRUS (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro (MFAG 10684)
- National Institutes of Health (DK091222,, DK042191, DK055812)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 091222, DK 055812, P01DK091222, R01DK055812, R01DK056762, R56DK042191, DK042191, R37DK042191, R01DK042191, R56DK055812, DK-056762)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- probiotics, VSL#3, ileitis, intestinal permeability, epithelial barrier function, TNF-α, tight junction proteins, claudin-2, occludin, paracellular permeability, inflammatory bowel disease
- MeSH terms
- Animals, Bacteria, Gene Expression Regulation, Homeostasis, Ileitis, Intestinal Mucosa, Permeability, Tumor Necrosis Factor-alpha, Receptors, Tumor Necrosis Factor, Tight Junctions, Probiotics, Mice
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