{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:49:57Z","timestamp":1785181797318,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Feder","award":["11319"],"award-info":[{"award-number":["11319"]}]},{"name":"Feder","award":["35372"],"award-info":[{"award-number":["35372"]}]},{"name":"Haus-de-France Regional grants","award":["11319"],"award-info":[{"award-number":["11319"]}]},{"name":"Haus-de-France Regional grants","award":["35372"],"award-info":[{"award-number":["35372"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Gut microbiota affect progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg of Lpps\/L, but not 0.25 and 1 mg of Lpps\/L, significantly alleviated RA symptoms in CIA DBA\/1OOaHsd mice. The arthritis index (AI) was also reduced in CAIA mice. In the CIA-protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher cecal and colon E. coli and lower caecal L. murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA-protected mice triggered by LPS secreted higher Il-10 than control ones. However, a higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs\u2019 recruitment. Labeled bacteria with the Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16 h post-gavage but not in Peyer\u2019s patches and the spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24 h. An FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.<\/jats:p>","DOI":"10.3390\/nu15234861","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T12:12:13Z","timestamp":1700568733000},"page":"4861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Gut\u2013Joint Axis: Impact of Bifidobacterial Cell Wall Lipoproteins on Arthritis Development"],"prefix":"10.3390","volume":"15","author":[{"given":"Frank","family":"Piva","sequence":"first","affiliation":[{"name":"Virology Laboratory-ULR3610, University of Lille and CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3709-957X","authenticated-orcid":false,"given":"Philippe","family":"Gervois","sequence":"additional","affiliation":[{"name":"Virology Laboratory-ULR3610, University of Lille and CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youness","family":"Karrout","sequence":"additional","affiliation":[{"name":"Inserm U1008, University of Lille and CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Famara","family":"San\u00e9","sequence":"additional","affiliation":[{"name":"Virology Laboratory-ULR3610, University of Lille and CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-8096","authenticated-orcid":false,"given":"Marie-B\u00e9n\u00e9dicte","family":"Romond","sequence":"additional","affiliation":[{"name":"Virology Laboratory-ULR3610, University of Lille and CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.molmed.2020.04.001","article-title":"The Gut Microbiota: Emerging Evidence in Autoimmune Diseases","volume":"26","author":"Zhang","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ruiz-Lim\u00f3n, P., Mena-V\u00e1zquez, N., Moreno-Indias, I., Manrique-Arija, S., Lisbona-Monta\u00f1ez, J.M., Cano-Garc\u00eda, L., Tinahones, F.J., and Fern\u00e1ndez-Nebro, A. (2022). Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113518"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/annrheumdis-2019-215743","article-title":"Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population","volume":"79","author":"Kishikawa","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/nm.3914","article-title":"The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment","volume":"21","author":"Zhang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"eabn4722","DOI":"10.1126\/scitranslmed.abn4722","article-title":"Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes","volume":"15","author":"Thompson","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1136\/ard.62.3.208","article-title":"An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis","volume":"62","author":"Hagfors","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"H\u00e4ger, J., Bang, H., Hagen, M., Frech, M., Tr\u00e4ger, P., Sokolova, M.V., Steffen, U., Tascilar, K., Sarter, K., and Schett, G. (2019). The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study. Nutrients, 11.","DOI":"10.3390\/nu11102392"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"H\u00e4upl, T., S\u00f6rensen, T., Smiljanovic, B., Darcy, M., Scheder-Bieschin, J., Steckhan, N., Hartmann, A.M., Koppold, D.A., Stuhlm\u00fcller, B., and Skriner, K. (2023). Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis. J. Clin. Med., 12.","DOI":"10.3390\/jcm12134359"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2174\/1874312901812010019","article-title":"Role of Diet in Influencing Rheumatoid Arthritis Disease Activity","volume":"12","author":"Badsha","year":"2018","journal-title":"Open Rheumatol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/rheumatology\/36.1.64","article-title":"Faecal microbial flora and disease activity in rheumatoid arthritis during a vegan diet","volume":"36","author":"Peltonen","year":"1997","journal-title":"Br. J. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/art.1780290413","article-title":"Suppressive effect of Escherichia coli on adjuvant-induced arthritis in germ-free rats","volume":"29","author":"Kohashi","year":"1986","journal-title":"Arthritis Rheum."},{"key":"ref_12","first-page":"415","article-title":"The role of humoral immunity in Lactobacillus casei cell wall induced arthritis","volume":"14","author":"Lehman","year":"1987","journal-title":"J. Rheumatol."},{"key":"ref_13","first-page":"1061","article-title":"Cell wall fragments from major residents of the human intestinal flora induce chronic arthritis in rats","volume":"16","author":"Severijnen","year":"1989","journal-title":"J. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1128\/IAI.68.6.3535-3540.2000","article-title":"Bacterial cell wall-induced arthritis: Chemical composition and tissue distribution of four Lactobacillus strains","volume":"68","author":"Simelyte","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1136\/ard.62.10.976","article-title":"Role of peptidoglycan subtypes in the pathogenesis of bacterial cell wall arthritis","volume":"62","author":"Simelyte","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0024-3205(98)00315-4","article-title":"Suppressive effects of the oral administration of Lactobacillus casei on type II collagen-induced arthritis in DBA\/1 mice","volume":"63","author":"Kato","year":"1998","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4315\/0362-028X-65.1.153","article-title":"Oral intake of Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 prevents collagen-induced arthritis in mice","volume":"65","author":"Kano","year":"2002","journal-title":"J. Food Prot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1093\/jn\/134.8.1964","article-title":"Lactobacillus GG bacteria ameliorate arthritis in Lewis rats","volume":"134","author":"Baharav","year":"2004","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1016\/j.molimm.2007.12.010","article-title":"Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effector functions","volume":"45","author":"So","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"680073","DOI":"10.3389\/fimmu.2021.680073","article-title":"Lactobacillus casei CCFM1074 Alleviates Collagen-Induced Arthritis in Rats via Balancing Treg\/Th17 and Modulating the Metabolites and Gut Microbiota","volume":"12","author":"Fan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pan, H., Guo, R., Ju, Y., Wang, Q., Zhu, J., Xie, Y., Zheng, Y., Li, T., Liu, Z., and Lu, L. (2019). A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis. Microbiome, 7.","DOI":"10.1186\/s40168-019-0719-1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1186\/s12967-020-02477-8","article-title":"Lactobacillus sakei suppresses collagen-induced arthritis and modulates the differentiation of T helper 17 cells and regulatory B cells","volume":"18","author":"Jhun","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yamashita, M., Matsumoto, K., Endo, T., Ukibe, K., Hosoya, T., Matsubara, Y., Nakagawa, H., Sakai, F., and Miyazaki, T. (2017). Preventive Effect of Lactobacillus helveticus SBT2171 on Collagen-Induced Arthritis in Mice. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01159"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1089\/jir.2016.0057","article-title":"Lactobacillus salivarius Isolated from Patients with Rheumatoid Arthritis Suppresses Collagen-Induced Arthritis and Increases Treg Frequency in Mice","volume":"36","author":"Liu","year":"2016","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Esvaran, M., and Conway, P.L. (2019). Lactobacillus fermentum PC1 has the Capacity to Attenuate Joint Inflammation in Collagen-Induced Arthritis in DBA\/1 Mice. Nutrients, 11.","DOI":"10.3390\/nu11040785"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1093\/rheumatology\/33.11.1030","article-title":"Intestinal flora in early rheumatoid arthritis","volume":"33","author":"Eerola","year":"1994","journal-title":"Br. J. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Ren, H., Yang, N., Xia, X., Chen, Q., Zhou, D., Liu, Z., Chen, X., Chen, Y., and Huang, W. (2023). Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis. Nutrients, 15.","DOI":"10.3390\/nu15020255"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14665","DOI":"10.1021\/acs.jafc.2c04602","article-title":"Bifidobacterium breve CCFM1078 Alleviates Collagen-Induced Arthritis in Rats via Modulating the Gut Microbiota and Repairing the Intestinal Barrier Damage","volume":"70","author":"Li","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"736196","DOI":"10.3389\/fimmu.2021.736196","article-title":"Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients with Different RF Levels","volume":"12","author":"Jeong","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/1756-185X.12333","article-title":"Effects of Lactobacillus casei supplementation on disease activity and inflammatory cytokines in rheumatoid arthritis patients: A randomized double-blind clinical trial","volume":"17","author":"Alipour","year":"2014","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00811","DOI":"10.1016\/j.idcr.2020.e00811","article-title":"Lactobacillus endocarditis: A case report in France and literature review","volume":"21","author":"Campagne","year":"2020","journal-title":"IDCases"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e01401","DOI":"10.1016\/j.idcr.2022.e01401","article-title":"Lactobacillus jensenii mitral valve endocarditis: Case report, literature review and new perspectives","volume":"27","author":"Rigamonti","year":"2022","journal-title":"IDCases"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00915","DOI":"10.1016\/j.idcr.2020.e00915","article-title":"Lactobacillus endocarditis in a healthy patient with probiotic use","volume":"22","author":"Pasala","year":"2020","journal-title":"IDCases"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mikucka, A., Deptu\u0142a, A., Bogiel, T., Chmielarczyk, A., Nurczy\u0144ska, E., and Gospodarek-Komkowska, E. (2022). Bacteraemia Caused by Probiotic Strains of Lacticaseibacillus rhamnosus-Case Studies Highlighting the Need for Careful Thought before Using Microbes for Health Benefits. Pathogens, 11.","DOI":"10.3390\/pathogens11090977"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.3168\/jds.S0022-0302(98)75683-8","article-title":"Cell-free whey from milk fermented with Bifidobacterium breve C50 used to modify the colonic microflora of healthy subjects","volume":"81","author":"Romond","year":"1998","journal-title":"J. Dairy Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.biochi.2014.10.007","article-title":"Bifidobacterium breve C50 secretes lipoprotein with CHAP domain recognized in aggregated form by TLR2","volume":"107 Pt B","author":"Scuotto","year":"2014","journal-title":"Biochimie"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.ijbiomac.2015.10.023","article-title":"In silico mining and characterization of bifidobacterial lipoprotein with CHAP domain secreted in an aggregated form","volume":"82","author":"Scuotto","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Sane, F., Piva, F., and Romond, M.B. (2023). Free lipoproteins from Bifidobacterium longum alleviate osteoarthritis through modulation of the gut microbiome. Microbiome Res. Rep., 2.","DOI":"10.20517\/mrr.2023.12"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nprot.2007.173","article-title":"Collagen-induced arthritis","volume":"2","author":"Brand","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"R158","DOI":"10.1186\/ar2838","article-title":"Regulation of pathogenic IL-17 responses in collagen-induced arthritis: Roles of endogenous interferon-gamma and IL-4","volume":"11","author":"Sarkar","year":"2009","journal-title":"Arthritis Res. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijantimicag.2017.03.010","article-title":"Bifidobacteria-derived lipoproteins inhibit the infection with coxsackievirus B4 in vitro","volume":"50","author":"Romond","year":"2017","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_42","first-page":"154","article-title":"Bifidobact\u00e9ries: De la bact\u00e9rie commensale aux probiotiques et m\u00e9tabiotiques\/postbiotiques","volume":"Volume 3","author":"Ghoul","year":"2023","journal-title":"G\u00e9nie des Proc\u00e9d\u00e9s Enzymatiques, Fermentaires et D\u2019encapsulation Appliqu\u00e9s Aux Industries Agro-Alimentaires"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/anae.1997.0090","article-title":"Cell-free wheys from bifidobacteria fermented milks exert a regulatory effect on the intestinal microflora of mice and humans","volume":"3","author":"Romond","year":"1997","journal-title":"Anaerobe"},{"key":"ref_44","unstructured":"Ghoul, M. (2023). Implementation of Enzymatic Processes and Lactic Acid Bacteria in Food Industry, ISTE. Chapter 8."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3168\/jds.S0022-0302(02)74205-7","article-title":"Partial Characterization of Bifidobacterium breve C50 Cell-Free Whey Compounds Inducing Modifications to the Intestinal Microflora","volume":"85","author":"Yazourh","year":"2002","journal-title":"J. Dairy Sci."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tolve, R., Cela, N., Condelli, N., Di Cairano, M., Caruso, M.C., and Galgano, F. (2020). Microencapsulation as a Tool for the Formulation of Functional Foods: The Phytosterols\u2019 Case Study. Foods, 9.","DOI":"10.3390\/foods9040470"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1002\/eji.201041374","article-title":"Thymic but not splenic CD8(+) DCs can efficiently cross-prime T cells in the absence of licensing factors","volume":"41","author":"Dresch","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.4049\/jimmunol.175.4.2579","article-title":"Interaction between Synovial Inflammatory Tissue and Bone Marrow in Rheumatoid Arthritis","volume":"175","author":"Redlich","year":"2005","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1002\/art.40225","article-title":"Therapeutic modulation of plasmacytoid dendritic cells in experimental Arthritis","volume":"69","author":"Nehmar","year":"2017","journal-title":"Arthritis Rheum."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1189\/jlb.0610342","article-title":"Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen presenting potential of plasmacytoid DCs","volume":"90","author":"Kool","year":"2011","journal-title":"J. Leuk. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nri3865","article-title":"The multifaceted biology of plasmacytoid dendritic cells","volume":"15","author":"Swiecki","year":"2015","journal-title":"Nat. Rev. Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:26:27Z","timestamp":1760131587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/23\/4861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":51,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["nu15234861"],"URL":"https:\/\/doi.org\/10.3390\/nu15234861","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,21]]}}}