Commensal and Probiotic Bacteria Influence Intestinal Barrier Function and Susceptibility to Colitis in Nod1−/−;Nod2−/− Mice
Abstract
BACKGROUND: The intestinal microbiota regulates key host functions. It is unknown whether modulation of the microbiota can affect a genetically determined host phenotype. Polymorphisms in the Nucleotide oligomerization domain (Nod)-like receptor family confer genetic risk for inflammatory bowel disease (IBD). We investigated whether the intestinal microbiota and the probiotic strain Bifidobacterium breve NCC2950 affect intestinal barrier function and responses to intestinal injury in Nod1(-/-); Nod2(-/-) mice. METHODS: Specific pathogen-free (SPF) Nod1(-/-); Nod2(-/-) mice and mice gnotobiotically derived with altered Schaedler flora (ASF) biota were used. SPF Nod1(+/-); Nod2(+/-) littermates (generated by crossing SPF Nod1(-/-); Nod2(-/-) and germ-free C57BL/6 mice) and ASF Nod1(+/-); Nod2(+/-) mice were used as controls. SPF mice were gavaged daily with 10(9) -CFU B. breve for 14 days before colitis induction. Denaturing gradient gel electrophoresis (DGGE) and real-time polymerase chain reaction (PCR) were used to assess microbiota composition. Intestinal permeability was assessed by in vitro and in vivo techniques. Expressions of epithelial apical junction proteins, mucin, and antimicrobial proteins were assessed by quantitative reverse-transcription PCR (qRT-PCR) and immunofluorescence. Responses to intestinal injury were investigated using an acute experimental model of colitis. RESULTS: Under SPF conditions, Nod1(-/-); Nod2(-/-) mice had increased paracellular permeability, decreased E-cadherin, and lower colonic antimicrobial RegIII-γ expression compared to Nod1(+/-); Nod2(+/-) littermate controls. These changes were associated with increased susceptibility to colitis. ASF colonization or B. breve supplementation normalized RegIII-γ expression and decreased susceptibility to dextran sodium sulfate (DSS) colitis in Nod1(-/-); Nod2(-/-) mice. CONCLUSIONS: The intestinal microbiota influences colitis severity in Nod1(-/-); Nod2(-/-) mice. The results suggest that colonization strategies with defined commensals or exogenous specific probiotic therapy may prevent intestinal inflammation in a genetically predisposed host.
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The gut microbiota have an important role in promoting the development, maintenance, and function of the intestinal barrier by increasing IgA production and mucin expression, preventing intestinal epithelial cell apoptosis, inhibiting colonization by enteric pathogens, and promoting physiological immune responses.
“The gut microbiota have an important role in promoting the development, maintenance, and function of the intestinal barrier by increasing IgA production and mucin expression, preventing intestinal epithelial cell apoptosis, inhibiting colonization by enteric pathogens, and promoting physiological immune responses (113, 173, 178).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [113]
NOD1 and NOD2 knockout mice exhibit increased paracellular permeability and are more susceptible to DSS colitis mediated intestinal injury.
“NOD1 and NOD2 knockout mice exhibit increased paracellular permeability and are reported to be more susceptible to DSS colitis mediated intestinal injury.177”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [177]
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Self-citation
- Authors
- Natividad, J. M. M., Petit, V., Huang, X., de Palma, G., Jury, J., Sanz, Y., Philpott, D., Garcia Rodenas, C. L., McCoy, K. D., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Consejo Superior de Investigaciones Científicas (ES)
- University of Toronto (CA)
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-08
- Volume
- 18
- Issue
- 8
- Pages
- 1434-1446
- ISSN
- 1078-0998 (ISSN-L)
- OpenAlex
- W2031502524
- Cited by
- 139
- References
- 58
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 10 · 2018: 11 · 2017: 10 · 2016: 13 · 2015: 10 · 2014: 15 · 2013: 15 · 2012: 11
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Funders
- McMaster University
- Crohn's and Colitis Foundation of Canada
- Ministerio de Ciencia e Innovación (CSD2007-00063)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut microbiota, NOD1
- MeSH terms
- Animals, Bacteria, Cell Membrane Permeability, Colitis, Female, Intestines, Male, Mice, Inbred C57BL, RNA, Messenger, Cadherins, Dextran Sulfate, Probiotics, Reverse Transcriptase Polymerase Chain Reaction, Mice, Nod2 Signaling Adaptor Protein, Nod1 Signaling Adaptor Protein, Metagenome
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