A Commensal Bifidobacterium longum Strain Prevents Gluten-Related Immunopathology in Mice through Expression of a Serine Protease Inhibitor
Open accessAbstract
Microbiota-modulating strategies, including probiotic administration, have been tested for the treatment of chronic gastrointestinal diseases despite limited information regarding their mechanisms of action. We previously demonstrated that patients with active celiac disease have decreased duodenal expression of elafin, a human serine protease inhibitor, and supplementation of elafin by a recombinant Lactococcus lactis strain prevents gliadin-induced immunopathology in the NOD/DQ8 mouse model of gluten sensitivity. The commensal probiotic strain Bifidobacterium longum NCC2705 produces a serine protease inhibitor (Srp) that exhibits immune-modulating properties. Here, we demonstrate that B. longum NCC2705, but not a srp knockout mutant, attenuates gliadin-induced immunopathology and impacts intestinal microbial composition in NOD/DQ8 mice. Our results highlight the beneficial effects of a serine protease inhibitor produced by commensal B. longum strains. IMPORTANCE Probiotic therapies have been widely used to treat gastrointestinal disorders with variable success and poor mechanistic insight. Delivery of specific anti-inflammatory molecules has been limited to the use of genetically modified organisms, which has raised some public and regulatory concerns. By examining a specific microbial product naturally expressed by a commensal bacterial strain, we provide insight into a mechanistic basis for the use of B. longum NCC2705 to help treat gluten-related disorders.
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A serine protease inhibitor produced by Bifidobacterium longum reduces gluten-induced immunopathology in a preclinical mouse model.
“Consistent with a pathogenic role of proteolytic activity in CeD, a serine protease inhibitor produced by Bifidobacterium longum reduces gluten-induced immunopathology in a preclinical mouse model.44”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [44]
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Metabolism of wheat proteins by intestinal microbes: Implications for wheat related disorders
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- Authors
- McCarville, J. L., Dong, J., Caminero, A., Bermudez-Brito, M., Jury, J., Murray, J. A., Duboux, S., Steinmann, M., Delley, M., Tangyu, M., Langella, P., Mercenier, A., Bergonzelli, G., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
- Mayo Clinic (US)
- Nestlé (Switzerland) (CH)
- AgroParisTech (FR)
- ORCID
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2017-10
- Volume
- 83
- Issue
- 19
- Pages
- 1-13
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC5601352
- OpenAlex
- W2742247528
- Cited by
- 71
- References
- 56
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 10 · 2019: 9 · 2018: 2 · 2017: 1
- FWCI
- 6.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (MOP#142773)
- Nestlé Health Science
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- Bifidobacterium longum, serine protease inhibitors, elafin, celiac disease, gluten sensitivity, probiotics, commensal bacteria, gut microbiota, anti-inflammatory mechanism
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