Cited by 376Probiotics and Fermented FoodsInflammatory Bowel DiseaseImmune Response and Inflammation

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Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide

Fernandez, E. M., Valenti, V., Rockel, C., Hermann, C., Pot, B., Boneca, I. G., Grangette, C.·2011·Gut

DOI 10.1136/gut.2010.232918

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Abstract

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been linked to a loss of tolerance towards the resident microflora. Therapeutic use of probiotics is known to be strain specific, but precise mechanisms remain unclear. The role of NOD2 signalling and the protective effect of Lactobacillus peptidoglycan (PGN) and derived muropeptides in experimental colitis were evaluated. METHODS: The anti-inflammatory capacity of lactobacilli and derived bacterial compounds was evaluated using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis model. The role of NOD2, MyD88 and interleukin 10 (IL-10) in this protection was studied using Nod2(-/-), MyD88(-/-) and Il10-deficient mice, while induction of regulatory dendritic cells (DCs) was monitored through the expansion of CD103(+) DCs in mesenteric lymph nodes or after adoptive transfer of bone marrow-derived DCs. The development of regulatory T cells was investigated by following the expansion of CD4(+)FoxP3(+) cells. High-performance liquid chromatography and mass spectrometry were used to analyse the PGN structural differences. RESULTS: The protective capacity of strain Lactobacillus salivarius Ls33 was correlated with a local IL-10 production and was abolished in Nod2-deficient mice. PGN purified from Ls33 rescued mice from colitis in an IL-10-dependent manner and favoured the development of CD103(+) DCs and CD4(+)Foxp3(+) regulatory T cells. In vitro Ls33 PGN induced IL-10-producing DCs able to achieve in vivo protection after adoptive transfer in a NOD2-dependent way. This protection was also correlated with an upregulation of the indoleamine 2,3-dioxygenase immunosuppressive pathway. The protective capacity was not obtained with PGN purified from a non-anti-inflammatory strain. Structural analysis of PGNs highlighted in Ls33 the presence of an additional muropeptide, M-tri-Lys. The synthesised ligand protected mice from colitis in a NOD2-dependent but MyD88-independent manner. CONCLUSIONS: The results indicated that PGN and derived muropeptides are active compounds in probiotic functionality and might represent a useful therapeutic strategy in IBD.

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Authors: Fernandez, E. M., Valenti, V., Rockel, C., Hermann, C., Pot, B., Boneca, I. G., & Grangette, C.
Affiliations: Centre National de la Recherche Scientifique (FR)
University of Konstanz (DE)
Inserm (FR)
Corresponding author: Grangette, C.
ORCID: Pot, B.
Boneca, I. G.
Grangette, C.
Venue: Gut
Publisher: BMJ
Published: 2011-04-06
Volume: 60
Issue: 8
Pages: 1050-1059
ISSN: 0017-5749 (ISSN-L)
DOI: 10.1136/gut.2010.232918
OpenAlex: W2160579940
Cited by: 376
References: 54
Citations by year: 2026: 8 · 2025: 17 · 2024: 25 · 2023: 25 · 2022: 28 · 2021: 27 · 2020: 29 · 2019: 25 · 2018: 20 · 2017: 20 · 2016: 19 · 2015: 28 · 2014: 27 · 2013: 28 · 2012: 33
FWCI: 49.08
Type: journal article
Language: en
Open access: closed
Locations: Gut (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
VUBIR (Vrije Universiteit Brussel) (submittedVersion)
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: Lactobacillus salivarius, peptidoglycan, muropeptides, NOD2, inflammatory bowel disease, experimental colitis, TNBS-induced colitis, IL-10, regulatory dendritic cells, regulatory T cells, MyD88, indoleamine 2,3-dioxygenase, probiotics, anti-inflammatory activity
MeSH terms: Animals, Chromatography, High Pressure Liquid, Colitis, Dendritic Cells, Disease Models, Animal, Immunity, Cellular, Immunologic Factors, Lactobacillus, Mice, Inbred BALB C, Mice, Inbred C57BL, Peptidoglycan, Interleukin-10, Probiotics, T-Lymphocytes, Regulatory, Mice, Nod2 Signaling Adaptor Protein, Myeloid Differentiation Factor 88

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Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide

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