The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Anti-inflammatory capacity of selected lactobacilli in experimental colitis is driven by NOD2-mediated recognition of a specific peptidoglycan-derived muropeptide
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Furthermore, muramyl dipeptide or peptidoglycan mediated activation of NOD2 is reported to negatively regulate TLR signaling and provide protection of wildtype mice against colitis.175,176”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [176]
In the citing paper
“The absence of NOD protein–mediated microbial sensing leads to a loss of gut barrier homeostasis and leads to increased susceptibility to gut inflammatory diseases.176”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [176]
Citations
Cites
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Hugot, J.-P., Chamaillard, M., Zouali, H., Lesage, S., Cézard, J.-P., Belaiche, J., Almer, S., Tysk, C., O'Morain, C. A., Gassull, M., et al. (2001) · Nature · doi:10.1038/35079107 · Cited by 5,591
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251
Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80119-3 · Cited by 3,680
Coombes, J. L., Siddiqui, K. R. R., Arancibia-Cárcamo, C. V., Hall, J. A., Sun, C., Belkaid, Y., & Powrie, F. M. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070590 · Cited by 2,708
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
the NIDDK IBD Genetics Consortium, Barrett, J. C., the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Hansoul, S., Nicolae, D. L., Cho, J. H., Duerr, R. H., Rioux, J. D., Brant, S. R., et al. (2008) · Nature Genetics · doi:10.1038/ng.175 · Cited by 2,593
Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., Lees, C. W., Balschun, T., Lee, J., Roberts, R., et al. (2010) · Nature Genetics · doi:10.1038/ng.717 · Cited by 2,520
Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) Detection
Girardin, S. E., Boneca, I. G., Viala, J., Chamaillard, M., Labigne-Roussel, A., Thomas, G. D., Philpott, D. J., & Sansonetti, P. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200651200 · Cited by 2,397
Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach
Manichanh, C., Rigottier-Gois, L., Bonnaud, E., Gloux, K., Pelletier, E., Frangeul, L., Nalin, R., Jarrin, C., Chardon, P., Marteau, P., et al. (2006) · Gut · doi:10.1136/gut.2005.073817 · Cited by 2,277
Kruis, W., Frič, P., Pokrotnieks, J., Lukáš, M., Fixa, B., Kaščák, M., Kamm, M. A., Weismueller, J., Beglinger, C., Stolte, M., et al. (2004) · Gut · doi:10.1136/gut.2003.037747 · Cited by 1,285
Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis
Bouskra, D., Brézillon, C., Bérard, M., Werts, C., Varona, R., Boneca, I. G., & Eberl, G. (2008) · Nature · doi:10.1038/nature07450 · Cited by 1,107
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Nenci, A., Becker, C., Wullaert, A., Gareus, R., Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C. F., Madison, B., et al. (2007) · Nature · doi:10.1038/nature05698 · Cited by 1,077
Kelly, D., Campbell, J. I., King, T. P., Grant, G., Jansson, E. Å., Coutts, A., Pettersson, S., & Conway, S. (2003) · Nature Immunology · doi:10.1038/ni1018 · Cited by 1,026
Definition of Phenotypic Characteristics of Childhood-Onset Inflammatory Bowel Disease
Limbergen, J. V., Russell, R. K., Drummond, H. E., Aldhous, M. C., Round, N. K., Nimmo, E. R., Smith, L. A., Gillett, P. M., McGrogan, P., Weaver, L. T., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.06.081 · Cited by 953
NOD2 is a negative regulator of Toll-like receptor 2–mediated T helper type 1 responses
Watanabe, T., Kitani, A., Murray, P. J., & Strober, W. (2004) · Nature Immunology · doi:10.1038/ni1092 · Cited by 864
VSL#3 Probiotic-Mixture Induces Remission in Patients with Active Ulcerative Colitis
Bibiloni, R., Fedorak, R. N., Tannock, G. W., Madsen, K. L., Gionchetti, P., Campieri, M., Simone, C. D., & Sartor, R. B. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.41794.x · Cited by 743
CD4+CD25+ TR Cells Suppress Innate Immune Pathology Through Cytokine-dependent Mechanisms
Maloy, K. J., Salaün, L., Cahill, R., Dougan, G., Saunders, N. J. S. G., & Powrie, F. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021345 · Cited by 740
Peptidoglycan Molecular Requirements Allowing Detection by Nod1 and Nod2
Girardin, S. E., Travassos, L. H., Hervé, M., Blanot, D., Boneca, I. G., Philpott, D. J., Sansonetti, P. J., & Mengin‐Lecreulx, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307198200 · Cited by 684
Bacterial contributions to mammalian gut development
Hooper, L. (2004) · Trends in Microbiology · doi:10.1016/j.tim.2004.01.001 · Cited by 541 · cited 1×
“INTRODUCTION Themicrobiota is in permanent interaction with the host epithelium and immune system and contributes to gastrointestinal health.(1) In genetically susceptible individuals, an inappropriate mucosal immune response against the intestinal flora appears to be the principal mechanism leading to the pathogenesi…”
BackgroundCommon variants at five new loci associated with early-onset inflammatory bowel disease
Imielinski, M. B., Baldassano, R. N., Griffiths, A. M., Russell, R. K., Annese, V., Dubinsky, M. C., Kugathasan, S., Bradfield, J. P., Walters, T. D., Abou‐Sleiman, P. M., et al. (2009) · Nature Genetics · doi:10.1038/ng.489 · Cited by 484
Structure–Function Relationship of Cytokine Induction by Lipoteichoic Acid fromStaphylococcus aureus
Morath, S., Geyer, A., & Härtung, T. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.3.393 · Cited by 476
Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis
Zocco, M. A., Verme, L. Z. D., Cremonini, F., Piscaglia, A. C., Nista, E. C., Candelli, M., Novi, M., Rigante, D., Cazzato, I. A., Ojetti, V., et al. (2006) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2006.02927.x · Cited by 472
Grangette, C., Nutten, S., Palumbo, E., Morath, S., Hermann, C., Dewulf, J., Pot, B., Härtung, T., Pascal Hols, A., & Mercenier, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504084102 · Cited by 443
Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria
Foligné, B. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i2.236 · Cited by 427
Marteau, P. R., Lémann, M., Seksik, P., Laharie, D., Colombel, J. F., Bouhnik, Y., Cadiot, G., Soulé, J. C., Bourreille, A., Metman, E.-H., et al. (2005) · Gut · doi:10.1136/gut.2005.076604 · Cited by 412
FAO Technical Meeting on Prebiotics
Piñeiro, M., Asp, N., Reid, G., Macfarlane, S., Morelli, L., Brunser, O., & Tuohy, K. M. (2008) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31817f184e · Cited by 402
Boneca, I. G., Dussurget, O., Cabanes, D., Nahori, M., Sousa, S., Lecuit, M., Psylinakis, E., Bouriotis, V., Hugot, J., Giovannini, M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609672104 · Cited by 378
Matteoli, G., Mazzini, E., Iliev, I. D., Mileti, E., Fallarino, F., Puccetti, P., Chieppa, M., & Rescigno, M. (2010) · Gut · doi:10.1136/gut.2009.185108 · Cited by 377
Role of NF-κB in immune and inflammatory responses in the gut
Neurath, M. F., Becker, C., & Barbulescu, K. (1998) · Gut · doi:10.1136/gut.43.6.856 · Cited by 349
Watanabe, T., Asano, N., Murray, P. J., Ozato, K., Tailor, P. B., Fuss, I. J., Kitani, A., & Strober, W. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33145 · Cited by 341
Petrof, E. O., Kojima, K., Ropeleski, M. J., Musch, M. W., Tao, Y., Simone, C. D., & Chang, E. B. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.09.001 · Cited by 330
A Key Role of Dendritic Cells in Probiotic Functionality
Foligné, B., Ζουμποπούλου, Γ., Dewulf, J., Younes‐Chennoufi, A. B., Chareyre, F., Sirard, J., Pot, B., & Grangette, C. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000313 · Cited by 292
Netea, M. G., Ferwerda, G., de Jong, D. J., Jansen, T., Jacobs, L., Kramer, M., Naber, A. H. J., Drenth, J. P. H., Girardin, S. E., Kullberg, B. J., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.6518 · Cited by 274
Regulatory T cells and intestinal homeostasis
Coombes, J. L., Robinson, N. J., Maloy, K. J., Uhlig, H. H., & Powrie, F. M. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00250.x · Cited by 273
Nods: a family of cytosolic proteins that regulate the host response to pathogens
Inohara, N. (2002) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(02)00289-8 · Cited by 240
Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice
Gurtner, G. J., Newberry, R. D., Schloemann, S. R., McDonald, K. G., & Stenson, W. F. (2003) · Gastroenterology · doi:10.1053/j.gastro.2003.08.031 · Cited by 226
Castillo, N. A., Perdigón, G., & de LeBlanc, A. D. M. (2011) · BMC Microbiology · doi:10.1186/1471-2180-11-177 · Cited by 211
The role of peptidoglycan in pathogenesis
Boneca, I. G. (2005) · Current Opinion in Microbiology · doi:10.1016/j.mib.2004.12.008 · Cited by 207
Uehara, A., Yang, S., Fujimoto, Y., Fukase, K., Kusumoto, S., Shibata, K., Sugawara, S., & Takada, H. (2004) · Cellular Microbiology · doi:10.1111/j.1462-5822.2004.00433.x · Cited by 197
Intestinal inflammation abrogates the tolerogenic properties of MLN CD103 + dendritic cells
Laffont, S., Siddiqui, K. R. R., & Powrie, F. M. (2010) · European Journal of Immunology · doi:10.1002/eji.200939957 · Cited by 193
Wang, J., Wu, Y., Yang, G., & Aksoy, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901226106 · Cited by 192
CARD15/NOD2 Is Required for Peyer's Patches Homeostasis in Mice
Barreau, F., Meinzer, U., Chareyre, F., Berrebi, D. D., Niwa‐Kawakita, M., Dussaillant, M., Foligné, B., Ollendorff, V., Heyman, M., Bonacorsi, S., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000523 · Cited by 144
Shida, K., Kiyoshima‐Shibata, J., Kaji, R., Nagaoka, M., & Nanno, M. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03095.x · Cited by 136
PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation
Dalmasso, G., Charrier‐Hisamuddin, L., Nguyen, H. T. T., Yan, Y., Sitaraman, S. V., & Merlin, D. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.026 · Cited by 122
PGLYRP-2 and Nod2 Are Both Required for Peptidoglycan-Induced Arthritis and Local Inflammation
Saha, S., Qi, J., Wang, S., Wang, M. H., Li, X., Kim, Y., Núñez, G., Gupta, D., & Dziarski, R. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2008.12.010 · Cited by 104
Foligné, B., Nutten, S., Steidler, L., Dennin, V., Goudercourt, D., Mercenier, A., & Pot, B. (2006) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-3143-x · Cited by 92
Courtin, P., Miranda, G., Guillot, A., Wessner, F., Mézange, C., Domakova, E., Kulakauskas, S., & Chapot, M.-P. (2006) · Journal of Bacteriology · doi:10.1128/jb.00285-06 · Cited by 89
Coquerelle, C., Oldenhove, G., Acolty, V., Denoeud, J., Vansanten, G., Verdebout, J., Mellor, A. L., Bluestone, J. A., & Moser, M. (2009) · Gut · doi:10.1136/gut.2008.162842 · Cited by 71
Coupling Toll-like receptor signaling with phagocytosis: potentiation of antigen presentation
Blander, J. M. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.11.001 · Cited by 68
Detailed Structural Analysis of the Peptidoglycan of the Human Pathogen Neisseria meningitidis
Antignac, A., Rousselle, J.-C., Namane, A., Labigne-Roussel, A., Taha, M., & Boneca, I. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304749200 · Cited by 60
Sato, T., Kanai∥, T., Watanabe, M., Sakuraba, A., Okamoto, S., Nakai, T., Okazawa, A., Inoue, N., Totsuka, T., Yamazaki, M., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2003.12.011 · Cited by 59
Bu, H., Wang, X., Tang, Y., Koti, V., & Tan, X. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21985 · Cited by 52
Harokopakis, E., Hajishengallis, G., Greenway, T., Russell, M. W., & Michalek, S. M. (1997) · Infection and Immunity · doi:10.1128/iai.65.4.1445-1454.1997 · Cited by 52
Charrière, G. M., Ip, W. E., Déjardin, S., Boyer, L., Sokolovska, A., Cappillino, M. P., Cherayil, B. J., Podolsky, D. K., Kobayashi, K. S., Silverman, N. S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.115584 · Cited by 46
VSL3 probiotic mixture induces remission in patients with active ulcerative colitis
Fedorak, R. N., Gionchetti, P., Campieri, M., Madsen, K., Isaacs, K. L., Desimone, C., & Sartor, R. B. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)81909-1 · Cited by 44
Flagged first, then by citations
Cited by
Sorted by citations
Hill (2014) · doi:10.1038/nrgastro.2014.66 · Cited by 9,592
Salminen, S., Collado, M. C., Endo, A., Hill, C., Lebeer, S., Quigley, E. M. M., Sanders, M. E., Shamir, R., Swann, J. R., Szajewska, H., et al. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00440-6 · Cited by 2,488
Swanson, K. S., Gibson, G. R., Hutkins, R., Reimer, R. A., Reid, G., Verbeke, K., Scott, K. P., Holscher, H. D., Azad, M. B., Delzenne, N. M., et al. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0344-2 · Cited by 2,196
The pros, cons, and many unknowns of probiotics
Suez, J., Zmora, N., Segal, E., & Elinav, E. (2019) · Nature Medicine · doi:10.1038/s41591-019-0439-x · Cited by 1,398
Probiotic Mechanisms of Action
Bermúdez-Brito, M., Plaza‐Díaz, J., Muñoz‐Quezada, S., Gómez‐Llorente, C., & Gil, Á. (2012) · Annals of Nutrition and Metabolism · doi:10.1159/000342079 · Cited by 1,326
Metadata
- 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.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2011-04-06
- Volume
- 60
- Issue
- 8
- Pages
- 1050-1059
- ISSN
- 0017-5749 (ISSN-L)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
