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Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice
Open accessAbstract
Background & aims Effective therapeutics for treating acute colitis, caused by disruption of the intestinal epithelial barrier, are scarce. Trefoil factors (TFF) are cytoprotective and promote epithelial wound healing and reconstitution of the gastrointestinal tract, which makes them good candidate therapeutics for acute colitis. However, orally administered TFF stick to the mucus of the small intestine and are absorbed at the cecum.Methods We have engineered the food-grade bacterium Lactococcus lactis to secrete bioactive murine TFF. The protective and therapeutic potentials of these TFF-secreting L. lactis were evaluated in parallel with purified TFF in the dextran sodium sulfate (DSS)-induced murine model for acute colitis and in established chronic colitis in interleukin (IL)-10(-/-) mice. Disease was evaluated by blinded macroscopic and microscopic inflammatory scores and by myeloperoxidase activity.Results Intragastric administration of TFF-secreting L. lactis led to active delivery of TFF at the mucosa of the colon and, in contrast to administration of purified TFF, proved to be very effective in prevention and healing of acute DSS-induced colitis. The in situ secreted murine TFF significantly decreased morbidity and mortality and stimulated prostaglandin-endoperoxide synthase 2 expression, which represents a major therapeutic pathway. In addition, this approach was successful in improving established chronic colitis in IL-10(-/-) mice.Conclusions We have positively evaluated a new therapeutic approach for acute and chronic colitis that involves in situ secretion of murine TFF by orally administered L. lactis. This novel approach may lead to effective management of acute and chronic colitis and epithelial damage in humans.
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“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
From Probiotics and the gut microbiota in intestinal health and disease (2010) · cites this paper as [123]
In the citing paper
“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
From Probiotics and the gut microbiota in intestinal health and disease (2010) · cites this paper as [123]
In the citing paper
“Instead of traditional orogastric administration of TFF, which sticks to the mucus layer in the small bowel preventing its localization in the colon, use of the recombinant bacterium enables delivery of TFF directly to the colonic mucosa and results in amelioration of DSS-induced disease in mice.123”
From Probiotics and the gut microbiota in intestinal health and disease (2010) · cites this paper as [123]
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Metadata
- Authors
- Vandenbroucke, K., Hans, W., Van Huysse, J., Neirynck, S., Demetter, P., Remaut, E., Rottiers, P., & Steidler, L.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- University College Cork (IE)
- Ghent University Hospital (BE)
- Corresponding author
- Steidler, Lothar
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 127
- Issue
- 2
- Pages
- 502-513
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2116185627
- Cited by
- 277
- References
- 50
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 12 · 2021: 13 · 2020: 17 · 2019: 9 · 2018: 14 · 2017: 7 · 2016: 4 · 2015: 13 · 2014: 9 · 2013: 13 · 2012: 8
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- trefoil factor, Lactococcus lactis, acute colitis, chronic colitis, IL-10 knockout mice, DSS-induced colitis, epithelial repair, intestinal epithelial barrier, cyclooxygenase-2, mucosal protection, engineered bacteria
- MeSH terms
- Trefoil Factor-2, Trefoil Factor-3, Acute Disease, Administration, Oral, Animals, Chronic Disease, Colitis, Female, Isoenzymes, Mice, Inbred BALB C, Mucins, Muscle Proteins, Neuropeptides, Peptides, Prostaglandin-Endoperoxide Synthases, Recombinant Proteins, Lactococcus lactis, Wound Healing, Genetic Therapy, Gene Expression Regulation, Enzymologic, Mice, Cyclooxygenase 2, In Vitro Techniques
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