{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:51:33Z","timestamp":1775832693006,"version":"3.50.1"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874038"],"award-info":[{"award-number":["81874038"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501431"],"award-info":[{"award-number":["81501431"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600506"],"award-info":[{"award-number":["81600506"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672422"],"award-info":[{"award-number":["81672422"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The human microbiome has attracted attention for its potential utility in precision medicine. Increasingly, more researchers are recognizing changes in intestinal microbiome can upset the balance between\u00a0pro-\u00a0and\u00a0anti-inflammatory\u00a0factors of host immune system, potentially contributing to arthritis immunopathogenesis. Patients who develop rheumatoid arthritis from undifferentiated arthritis can face multiple irreversible joint lesions and even deformities. Strategies for identifying undifferentiated arthritis patients who have a tendency to develop rheumatoid arthritis and interventions to prevent rheumatoid arthritis development are urgently needed. Intestinal microbiome dysbiosis and shifts in the miRNA profile affect undifferentiated arthritis progression, and may play an important role in rheumatoid arthritis pathophysiologic process via stimulating inflammatory cytokines and disturbing host and microbial metabolic functions. However, a causal relationship between microbiome\u2013miRNA interactions and rheumatoid arthritis development from undifferentiated arthritis has\u00a0not\u00a0been uncovered\u00a0yet. Changes in the intestinal microbiome and miRNA profiles of undifferentiated arthritis patients with different disease outcomes should be studied together to uncover the role of the intestinal microbiome in rheumatoid arthritis development and to identify potential prognostic indicators of rheumatoid arthritis in undifferentiated arthritis patients. Herein, we discuss the possibility of microbiome\u2013miRNA interactions contributing to rheumatoid arthritis development and describe the gaps in knowledge regarding their influence on undifferentiated arthritis prognosis that should be addressed by future studies.<\/jats:p>","DOI":"10.1007\/s00296-021-04798-3","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T12:26:08Z","timestamp":1618489568000},"page":"1567-1575","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Microbiome\u2013miRNA interactions in the progress from undifferentiated arthritis to rheumatoid arthritis: evidence, hypotheses, and opportunities"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2886-5615","authenticated-orcid":false,"given":"Haifeng","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2920-2741","authenticated-orcid":false,"given":"Yujun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-2388","authenticated-orcid":false,"given":"Jiezuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-9548","authenticated-orcid":false,"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-0593","authenticated-orcid":false,"given":"Lanjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"issue":"6","key":"4798_CR1","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/nri2094","volume":"7","author":"IB McInnes","year":"2007","unstructured":"McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7(6):429\u2013442","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"4798_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1136\/ard.2005.038471","volume":"65","author":"J van Aken","year":"2006","unstructured":"van Aken J, van Dongen H, le Cessie S, Allaart CF, Breedveld FC, Huizinga TW (2006) Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study. Ann Rheum Dis 65(1):20\u201325","journal-title":"Ann Rheum Dis"},{"issue":"6","key":"4798_CR3","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1097\/RHU.0000000000000280","volume":"21","author":"A Ramagli","year":"2015","unstructured":"Ramagli A, Corbacho I, Linhares F, de Abreu P, Teijeiro R, Garau M et al (2015) Characteristics of patients with early-onset arthritis in Latin America: description of the REPANARC cohort. J Clin Rheumatol 21(6):283\u2013288","journal-title":"J Clin Rheumatol"},{"issue":"11","key":"4798_CR4","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1007\/s00296-013-2799-8","volume":"33","author":"D Chen","year":"2013","unstructured":"Chen D, Li H, Liang L, Xiao Y, Xu T, Qiu Q et al (2013) Clinical features and independent predictors in the further development of rheumatoid arthritis in undifferentiated arthritis. Rheumatol Int 33(11):2827\u20132832","journal-title":"Rheumatol Int"},{"issue":"5","key":"4798_CR5","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1136\/annrheumdis-2011-200990","volume":"71","author":"DM Gerlag","year":"2012","unstructured":"Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR et al (2012) EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis 71(5):638\u2013641","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"4798_CR6","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.semarthrit.2013.08.005","volume":"43","author":"E McNally","year":"2014","unstructured":"McNally E, Keogh C, Galvin R, Fahey T (2014) Diagnostic accuracy of a clinical prediction rule (CPR) for identifying patients with recent-onset undifferentiated arthritis who are at a high risk of developing rheumatoid arthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 43(4):498\u2013507","journal-title":"Semin Arthritis Rheum"},{"issue":"6","key":"4798_CR7","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.reuma.2014.01.007","volume":"10","author":"A Arana-Guajardo","year":"2014","unstructured":"Arana-Guajardo A, Perez-Barbosa L, Vega-Morales D, Riega-Torres J, Esquivel-Valerio J, Garza-Elizondo M (2014) Application of a prediction model for the progression of rheumatoid arthritis in patients with undifferentiated arthritis. Reumatol Clin 10(6):360\u2013363","journal-title":"Reumatol Clin"},{"issue":"2","key":"4798_CR8","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3899\/jrheum.160693","volume":"44","author":"GH Brinkmann","year":"2017","unstructured":"Brinkmann GH, Norli ES, Kvien TK, Haugen AJ, Grovle L, Nygaard H et al (2017) Disease characteristics and rheumatoid arthritis development in patients with early undifferentiated arthritis: a 2-year followup study. J Rheumatol 44(2):154\u2013161","journal-title":"J Rheumatol"},{"issue":"11","key":"4798_CR9","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1002\/art.1780301102","volume":"30","author":"PK Gregersen","year":"1987","unstructured":"Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30(11):1205\u20131213","journal-title":"Arthritis Rheum"},{"key":"4798_CR10","doi-asserted-by":"publisher","first-page":"102400","DOI":"10.1016\/j.jaut.2019.102400","volume":"110","author":"HU Scherer","year":"2020","unstructured":"Scherer HU, H\u00e4upl T, Burmester GR (2020) The etiology of rheumatoid arthritis. J Autoimmun 110:102400","journal-title":"J Autoimmun"},{"issue":"10","key":"4798_CR11","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/nm.4185","volume":"22","author":"BO Schroeder","year":"2016","unstructured":"Schroeder BO, Backhed F (2016) Signals from the gut microbiota to distant organs in physiology and disease. Nat Med 22(10):1079\u20131089","journal-title":"Nat Med"},{"issue":"4","key":"4798_CR12","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.cell.2014.03.006","volume":"157","author":"N Gagliani","year":"2014","unstructured":"Gagliani N, Hu B, Huber S, Elinav E, Flavell RA (2014) The fire within: microbes inflame tumors. Cell 157(4):776\u2013783","journal-title":"Cell"},{"issue":"7516","key":"4798_CR13","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nature13568","volume":"513","author":"N Qin","year":"2014","unstructured":"Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L et al (2014) Alterations of the human gut microbiome in liver cirrhosis. Nature 513(7516):59\u201364","journal-title":"Nature"},{"issue":"8","key":"4798_CR14","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1097\/TP.0000000000000334","volume":"98","author":"Z Ren","year":"2014","unstructured":"Ren Z, Jiang J, Lu H, Chen X, He Y, Zhang H et al (2014) Intestinal microbial variation may predict early acute rejection after liver transplantation in rats. Transplantation 98(8):844\u2013852","journal-title":"Transplantation"},{"issue":"6","key":"4798_CR15","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1136\/gutjnl-2017-315084","volume":"68","author":"Z Ren","year":"2019","unstructured":"Ren Z, Li A, Jiang J, Zhou L, Yu Z, Lu H et al (2019) Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut 68(6):1014\u20131023","journal-title":"Gut"},{"issue":"11","key":"4798_CR16","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1007\/s00467-016-3527-x","volume":"32","author":"P Evenepoel","year":"2017","unstructured":"Evenepoel P, Poesen R, Meijers B (2017) The gut-kidney axis. Pediatr Nephrol 32(11):2005\u20132014","journal-title":"Pediatr Nephrol"},{"issue":"1","key":"4798_CR17","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1080\/1040841X.2016.1176988","volume":"43","author":"Y He","year":"2017","unstructured":"He Y, Wen Q, Yao F, Xu D, Huang Y, Wang J (2017) Gut-lung axis: the microbial contributions and clinical implications. Crit Rev Microbiol 43(1):81\u201395","journal-title":"Crit Rev Microbiol"},{"issue":"8","key":"4798_CR18","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/nm.3914","volume":"21","author":"X Zhang","year":"2015","unstructured":"Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D et al (2015) The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med 21(8):895\u2013905","journal-title":"Nat Med"},{"key":"4798_CR19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/ijms19102938","volume":"19","author":"A Picchianti-Diamanti","year":"2018","unstructured":"Picchianti-Diamanti A, Panebianco C, Salemi S, Sorgi ML, Di Rosa R, Tropea A et al (2018) Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept. Int J Mol Sci 19:10","journal-title":"Int J Mol Sci"},{"issue":"11","key":"4798_CR20","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.trecan.2019.08.003","volume":"5","author":"J Dong","year":"2019","unstructured":"Dong J, Tai JW, Lu LF (2019) miRNA-Microbiota interaction in gut homeostasis and colorectal cancer. Trends Cancer 5(11):666\u2013669","journal-title":"Trends Cancer"},{"issue":"3","key":"4798_CR21","doi-asserted-by":"publisher","first-page":"211","DOI":"10.5114\/fn.2019.88449","volume":"57","author":"P Alexandrov","year":"2019","unstructured":"Alexandrov P, Zhai Y, Li W, Lukiw W (2019) Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain. Folia Neuropathol 57(3):211\u2013219","journal-title":"Folia Neuropathol"},{"issue":"7488","key":"4798_CR22","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature12873","volume":"506","author":"Y Okada","year":"2014","unstructured":"Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K et al (2014) Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506(7488):376\u2013381","journal-title":"Nature"},{"issue":"4","key":"4798_CR23","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/ng1206","volume":"34","author":"A Suzuki","year":"2003","unstructured":"Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M et al (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34(4):395\u2013402","journal-title":"Nat Genet"},{"issue":"6","key":"4798_CR24","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nrrheum.2015.7","volume":"11","author":"K Yamamoto","year":"2015","unstructured":"Yamamoto K, Okada Y, Suzuki A, Kochi Y (2015) Genetics of rheumatoid arthritis in Asia\u2014present and future. Nat Rev Rheumatol 11(6):375\u2013379","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"4798_CR25","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1177\/1470320313478285","volume":"16","author":"GG Song","year":"2015","unstructured":"Song GG, Bae SC, Kim JH, Lee YH (2015) The angiotensin-converting enzyme insertion\/deletion polymorphism and susceptibility to rheumatoid arthritis, vitiligo and psoriasis: a meta-analysis. J Renin Angiotensin Aldosterone Syst 16(1):195\u2013202","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"issue":"9","key":"4798_CR26","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1038\/ng.3379","volume":"47","author":"TL Lenz","year":"2015","unstructured":"Lenz TL, Deutsch AJ, Han B, Hu X, Okada Y, Eyre S et al (2015) Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases. Nat Genet 47(9):1085\u20131090","journal-title":"Nat Genet"},{"issue":"1","key":"4798_CR27","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1172\/JCI32639","volume":"118","author":"S Abdollahi-Roodsaz","year":"2008","unstructured":"Abdollahi-Roodsaz S, Joosten LA, Koenders MI, Devesa I, Roelofs MF, Radstake TR et al (2008) Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest 118(1):205\u2013216","journal-title":"J Clin Invest"},{"issue":"6","key":"4798_CR28","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.immuni.2010.06.001","volume":"32","author":"HJ Wu","year":"2010","unstructured":"Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y et al (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32(6):815\u2013827","journal-title":"Immunity"},{"key":"4798_CR29","doi-asserted-by":"publisher","first-page":"6145810","DOI":"10.1155\/2016\/6145810","volume":"2016","author":"R Kugyelka","year":"2016","unstructured":"Kugyelka R, Kohl Z, Olasz K, Mikecz K, Rauch TA, Glant TT et al (2016) Enigma of IL-17 and Th17 cells in rheumatoid arthritis and in autoimmune animal models of arthritis. Mediators Inflamm 2016:6145810","journal-title":"Mediators Inflamm"},{"key":"4798_CR30","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fimmu.2012.00129","volume":"3","author":"AK Marwaha","year":"2012","unstructured":"Marwaha AK, Leung NJ, McMurchy AN, Levings MK (2012) TH17 cells in autoimmunity and immunodeficiency: protective or pathogenic? Front Immunol 3:129","journal-title":"Front Immunol"},{"issue":"1","key":"4798_CR31","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12864-019-5510-y","volume":"20","author":"Q Wang","year":"2019","unstructured":"Wang Q, Xu R (2019) Data-driven multiple-level analysis of gut-microbiome-immune-joint interactions in rheumatoid arthritis. BMC Genomics 20(1):124","journal-title":"BMC Genomics"},{"key":"4798_CR32","doi-asserted-by":"publisher","first-page":"e01202","DOI":"10.7554\/eLife.01202","volume":"2","author":"JU Scher","year":"2013","unstructured":"Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C et al (2013) Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2:e01202","journal-title":"Elife"},{"key":"4798_CR33","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/jcm6060060","volume":"6","author":"Y Maeda","year":"2017","unstructured":"Maeda Y, Takeda K (2017) Role of gut microbiota in rheumatoid arthritis. J Clin Med 6:6","journal-title":"J Clin Med"},{"issue":"1","key":"4798_CR34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13073-016-0299-7","volume":"8","author":"J Chen","year":"2016","unstructured":"Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J et al (2016) An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med 8(1):43","journal-title":"Genome Med"},{"issue":"2","key":"4798_CR35","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41577-019-0252-2","volume":"20","author":"WS Garrett","year":"2020","unstructured":"Garrett WS (2020) Immune recognition of microbial metabolites. Nat Rev Immunol 20(2):91\u201392","journal-title":"Nat Rev Immunol"},{"key":"4798_CR36","first-page":"5","volume":"2020","author":"L Ma","year":"2020","unstructured":"Ma L, Li H, Hu J, Zheng J, Zhou J, Botchlett R et al (2020) Indole alleviates diet-induced hepatic steatosis and inflammation in a manner involving myeloid cell PFKFB3. Hepatology 2020:5","journal-title":"Hepatology"},{"issue":"4","key":"4798_CR37","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1002\/hep.24525","volume":"54","author":"YD Wang","year":"2011","unstructured":"Wang YD, Chen WD, Yu D, Forman BM, Huang W (2011) The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) in mice. Hepatology 54(4):1421\u20131432","journal-title":"Hepatology"},{"key":"4798_CR38","doi-asserted-by":"publisher","first-page":"646","DOI":"10.3389\/fphys.2016.00646","volume":"7","author":"C Guo","year":"2016","unstructured":"Guo C, Chen WD, Wang YD (2016) TGR5, not only a metabolic regulator. Front Physiol 7:646","journal-title":"Front Physiol"},{"issue":"7790","key":"4798_CR39","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","volume":"577","author":"X Song","year":"2020","unstructured":"Song X, Sun X, Oh SF, Wu M, Zhang Y, Zheng W et al (2020) Microbial bile acid metabolites modulate gut RORgamma(+) regulatory T cell homeostasis. Nature 577(7790):410\u2013415","journal-title":"Nature"},{"key":"4798_CR40","first-page":"18","volume":"2019","author":"S Hang","year":"2019","unstructured":"Hang S, Paik D, Yao L, Kim E, Jamma T, Lu J et al (2019) Bile acid metabolites control TH17 and Treg cell differentiation. Nature 2019:18","journal-title":"Nature"},{"issue":"7\u20138","key":"4798_CR41","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1007\/s10495-019-01548-6","volume":"24","author":"P Dinesh","year":"2019","unstructured":"Dinesh P, Rasool M (2019) Berberine mitigates IL-21\/IL-21R mediated autophagic influx in fibroblast-like synoviocytes and regulates Th17\/Treg imbalance in rheumatoid arthritis. Apoptosis 24(7\u20138):644\u2013661","journal-title":"Apoptosis"},{"issue":"1","key":"4798_CR42","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/BOR.0000000000000681","volume":"32","author":"LJ Favazzo","year":"2020","unstructured":"Favazzo LJ, Hendesi H, Villani DA, Soniwala S, Dar QA, Schott EM et al (2020) The gut microbiome-joint connection: implications in osteoarthritis. Curr Opin Rheumatol 32(1):92\u2013101","journal-title":"Curr Opin Rheumatol"},{"issue":"1","key":"4798_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/femsre\/fuy035","volume":"43","author":"EM du Teil","year":"2019","unstructured":"du Teil EM, Gabarrini G, Harmsen HJM, Westra J, van Winkelhoff AJ, van Dijl JM (2019) Talk to your gut: the oral-gut microbiome axis and its immunomodulatory role in the etiology of rheumatoid arthritis. FEMS Microbiol Rev 43(1):1\u201318","journal-title":"FEMS Microbiol Rev"},{"issue":"1","key":"4798_CR44","doi-asserted-by":"publisher","first-page":"101473","DOI":"10.1016\/j.berh.2019.101473","volume":"34","author":"MF Konig","year":"2020","unstructured":"Konig MF (2020) The microbiome in autoimmune rheumatic disease. Best Pract Res Clin Rheumatol 34(1):101473","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"4798_CR45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bcp.2016.03.017","volume":"114","author":"E Alvarez-Curto","year":"2016","unstructured":"Alvarez-Curto E, Milligan G (2016) Metabolism meets immunity: The role of free fatty acid receptors in the immune system. Biochem Pharmacol 114:3\u201313","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"4798_CR46","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1186\/s12876-020-01444-3","volume":"20","author":"F Ambrozkiewicz","year":"2020","unstructured":"Ambrozkiewicz F, Karczmarski J, Kulecka M, Paziewska A, Niemira M, Zeber-Lubecka N et al (2020) In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn\u2019s disease\u2014a preliminary study. BMC Gastroenterol 20(1):307","journal-title":"BMC Gastroenterol"},{"issue":"1","key":"4798_CR47","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/s41598-017-00522-z","volume":"7","author":"W Wu","year":"2017","unstructured":"Wu W, He A, Wen Y, Xiao X, Hao J, Zhang F et al (2017) Comparison of microRNA expression profiles of Kashin-Beck disease, osteoarthritis and rheumatoid arthritis. Sci Rep 7(1):540","journal-title":"Sci Rep"},{"key":"4798_CR48","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1042\/BSR20193160","volume":"40","author":"J Wen","year":"2020","unstructured":"Wen J, Liu J, Zhang P, Jiang H, Xin L, Wan L et al (2020) RNA-seq reveals the circular RNA and miRNA expression profile of peripheral blood mononuclear cells in patients with rheumatoid arthritis. Biosci Rep 40:4","journal-title":"Biosci Rep"},{"issue":"6","key":"4798_CR49","first-page":"355","volume":"119","author":"C Luo","year":"2018","unstructured":"Luo C, Liang JS, Gong J, Zhang HL, Feng ZJ, Yang HT et al (2018) miRNA-31 over-expression improve synovial cells apoptosis induced by RA. Bratisl Lek Listy 119(6):355\u2013360","journal-title":"Bratisl Lek Listy"},{"issue":"1","key":"4798_CR50","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1186\/s13075-017-1465-z","volume":"19","author":"NS Lai","year":"2017","unstructured":"Lai NS, Yu HC, Tung CH, Huang KY, Huang HB, Lu MC (2017) The role of aberrant expression of T cell miRNAs affected by TNF-alpha in the immunopathogenesis of rheumatoid arthritis. Arthritis Res Ther 19(1):261","journal-title":"Arthritis Res Ther"},{"key":"4798_CR51","doi-asserted-by":"publisher","first-page":"144081","DOI":"10.1016\/j.gene.2019.144081","volume":"720","author":"MF Romo-Garcia","year":"2019","unstructured":"Romo-Garcia MF, Bastian Y, Zapata-Zuniga M, Macias-Segura N, Castillo-Ortiz JD, Lara-Ramirez EE et al (2019) Identification of putative miRNA biomarkers in early rheumatoid arthritis by genome-wide microarray profiling: a pilot study. Gene 720:144081","journal-title":"Gene"},{"issue":"1","key":"4798_CR52","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12891-020-3159-y","volume":"21","author":"HY Meng","year":"2020","unstructured":"Meng HY, Chen LQ, Chen LH (2020) The inhibition by human MSCs-derived miRNA-124a overexpression exosomes in the proliferation and migration of rheumatoid arthritis-related fibroblast-like synoviocyte cell. BMC Musculoskelet Disord 21(1):150","journal-title":"BMC Musculoskelet Disord"},{"issue":"5","key":"4798_CR53","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00005-018-0513-y","volume":"66","author":"M Ciechomska","year":"2018","unstructured":"Ciechomska M, Bonek K, Merdas M, Zarecki P, Swierkot J, Gluszko P et al (2018) Changes in MiRNA-5196 expression as a potential biomarker of anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis patients. Arch Immunol Ther Exp (Warsz) 66(5):389\u2013397","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"issue":"11\u201312","key":"4798_CR54","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s10495-018-1474-7","volume":"23","author":"J Gao","year":"2018","unstructured":"Gao J, Kong R, Zhou X, Ji L, Zhang J, Zhao D (2018) MiRNA-126 expression inhibits IL-23R mediated TNF-alpha or IFN-gamma production in fibroblast-like synoviocytes in a mice model of collagen-induced rheumatoid arthritis. Apoptosis 23(11\u201312):607\u2013615","journal-title":"Apoptosis"},{"key":"4798_CR55","first-page":"5","volume":"39","author":"D Li","year":"2019","unstructured":"Li D, Zhou Q, Hu G, Wang G (2019) MiRNA-506 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targetting TLR4. Biosci Rep 39:5","journal-title":"Biosci Rep"},{"issue":"1","key":"4798_CR56","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bbrc.2019.08.092","volume":"519","author":"L Shao","year":"2019","unstructured":"Shao L, Hou C (2019) miR-138 activates NF-kappaB signaling and PGRN to promote rheumatoid arthritis via regulating HDAC4. Biochem Biophys Res Commun 519(1):166\u2013171","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"4798_CR57","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.1111\/1756-185X.13202","volume":"20","author":"LC Su","year":"2017","unstructured":"Su LC, Huang AF, Jia H, Liu Y, Xu WD (2017) Role of microRNA-155 in rheumatoid arthritis. Int J Rheum Dis 20(11):1631\u20131637","journal-title":"Int J Rheum Dis"},{"issue":"1","key":"4798_CR58","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s13075-019-1920-0","volume":"21","author":"Y Cai","year":"2019","unstructured":"Cai Y, Jiang C, Zhu J, Xu K, Ren X, Xu L et al (2019) miR-449a inhibits cell proliferation, migration, and inflammation by regulating high-mobility group box protein 1 and forms a mutual inhibition loop with Yin Yang 1 in rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Res Ther 21(1):134","journal-title":"Arthritis Res Ther"},{"key":"4798_CR59","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s11658-018-0130-0","volume":"24","author":"L Liu","year":"2019","unstructured":"Liu L, Zuo Y, Xu Y, Zhang Z, Li Y, Pang J (2019) MiR-613 inhibits proliferation and invasion and induces apoptosis of rheumatoid arthritis synovial fibroblasts by direct down-regulation of DKK1. Cell Mol Biol Lett 24:8","journal-title":"Cell Mol Biol Lett"},{"issue":"11","key":"4798_CR60","first-page":"4850","volume":"23","author":"SP Qu","year":"2019","unstructured":"Qu SP, Li GW, Ma H, Xing Q (2019) MicroRNA-193a-3p participates in the progression of rheumatoid arthritis by regulating proliferation and apoptosis of MH7A cells through targeting IGFBP5. Eur Rev Med Pharmacol Sci 23(11):4850\u20134857","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"4798_CR61","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fmed.2018.00186","volume":"5","author":"S Alivernini","year":"2018","unstructured":"Alivernini S, Tolusso B, Petricca L, Bui L, Di Mario C, Gigante MR et al (2018) Synovial predictors of differentiation to definite arthritis in patients with seronegative undifferentiated peripheral inflammatory arthritis: microRNA signature, histological, and ultrasound features. Front Med (Lausanne) 5:186","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"4798_CR62","doi-asserted-by":"publisher","first-page":"10","DOI":"10.5114\/reum.2018.74742","volume":"56","author":"W Kurowska","year":"2018","unstructured":"Kurowska W, Kuca-Warnawin E, Radzikowska A, Jakubaszek M, Maslinska M, Kwiatkowska B et al (2018) Monocyte-related biomarkers of rheumatoid arthritis development in undifferentiated arthritis patients\u2014a pilot study. Reumatologia 56(1):10\u201316","journal-title":"Reumatologia"},{"issue":"17","key":"4798_CR63","doi-asserted-by":"publisher","first-page":"e19971","DOI":"10.1097\/MD.0000000000019971","volume":"99","author":"X Zhang","year":"2020","unstructured":"Zhang X, Cai H, Zhu M, Qian Y, Lin S, Li X (2020) Circulating microRNAs as biomarkers for severe coronary artery disease. Med (Baltim) 99(17):e19971","journal-title":"Med (Baltim)"},{"key":"4798_CR64","doi-asserted-by":"publisher","first-page":"e8943","DOI":"10.7717\/peerj.8943","volume":"8","author":"L Jin","year":"2020","unstructured":"Jin L, Zhang N, Zhang Q, Ding G, Yang Z, Zhang Z (2020) Serum microRNAs as potential new biomarkers for cisplatin resistance in gastric cancer patients. PeerJ 8:e8943","journal-title":"PeerJ"},{"issue":"3","key":"4798_CR65","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s40291-020-00464-9","volume":"24","author":"B Roy","year":"2020","unstructured":"Roy B, Yoshino Y, Allen L, Prall K, Schell G, Dwivedi Y (2020) Exploiting circulating MicroRNAs as biomarkers in psychiatric disorders. Mol Diagn Ther 24(3):279\u2013298","journal-title":"Mol Diagn Ther"},{"key":"4798_CR66","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13075-015-0555-z","volume":"17","author":"C Castro-Villegas","year":"2015","unstructured":"Castro-Villegas C, Perez-Sanchez C, Escudero A, Filipescu I, Verdu M, Ruiz-Limon P et al (2015) Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFalpha. Arthritis Res Ther 17:49","journal-title":"Arthritis Res Ther"},{"issue":"3","key":"4798_CR67","doi-asserted-by":"publisher","first-page":"R81","DOI":"10.1186\/ar3006","volume":"12","author":"J Li","year":"2010","unstructured":"Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y et al (2010) Altered microRNA expression profile with miR-146a up-regulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther 12(3):R81","journal-title":"Arthritis Res Ther"},{"issue":"6285","key":"4798_CR68","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1126\/science.aad3369","volume":"352","author":"A Zhernakova","year":"2016","unstructured":"Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T et al (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352(6285):565\u2013569","journal-title":"Science"},{"issue":"6285","key":"4798_CR69","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1126\/science.aad3503","volume":"352","author":"G Falony","year":"2016","unstructured":"Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K et al (2016) Population-level analysis of gut microbiome variation. Science 352(6285):560\u2013564","journal-title":"Science"},{"issue":"1","key":"4798_CR70","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s40168-017-0321-3","volume":"5","author":"AE Hoban","year":"2017","unstructured":"Hoban AE, Stilling RM, Moloney RD, Shanahan F, Dinan TG et al (2017) Microbial regulation of microRNA expression in the amygdala and prefrontal cortex. Microbiome 5(1):102","journal-title":"Microbiome"},{"key":"4798_CR71","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1126\/scitranslmed.aav1892","volume":"11","author":"AT Virtue","year":"2019","unstructured":"Virtue AT, McCright SJ, Wright JM, Jimenez MT, Mowel WK, Kotzin JJ et al (2019) The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs. Sci Transl Med 11:496","journal-title":"Sci Transl Med"},{"issue":"5","key":"4798_CR72","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1016\/j.cell.2019.01.037","volume":"176","author":"P Seth","year":"2019","unstructured":"Seth P, Hsieh PN, Jamal S, Wang L, Gygi SP, Jain MK et al (2019) Regulation of MicroRNA machinery and development by interspecies S-nitrosylation. Cell 176(5):1014\u20131025","journal-title":"Cell"},{"issue":"1","key":"4798_CR73","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.chom.2015.12.005","volume":"19","author":"S Liu","year":"2016","unstructured":"Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L et al (2016) The host shapes the gut microbiota via fecal microRNA. Cell Host Microbe 19(1):32\u201343","journal-title":"Cell Host Microbe"},{"key":"4798_CR74","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3389\/fnins.2019.00113","volume":"13","author":"C Hewel","year":"2019","unstructured":"Hewel C, Kaiser J, Wierczeiko A, Linke J, Reinhardt C, Endres K et al (2019) Common miRNA patterns of Alzheimer\u2019s disease and Parkinson\u2019s disease and their putative impact on commensal gut microbiota. Front Neurosci 13:113","journal-title":"Front Neurosci"},{"issue":"1","key":"4798_CR75","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s10020-020-00234-7","volume":"26","author":"M Li","year":"2020","unstructured":"Li M, Chen WD, Wang YD (2020) The roles of the gut microbiota-miRNA interaction in the host pathophysiology. Mol Med 26(1):101","journal-title":"Mol Med"},{"issue":"6","key":"4798_CR76","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/S0002-9343(01)00872-5","volume":"111","author":"LR Lard","year":"2001","unstructured":"Lard LR, Visser H, Speyer I, vander Horst-Bruinsma IE, Zwinderman AH, Breedveld FC et al (2001) Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 111(6):446\u2013451","journal-title":"Am J Med"},{"issue":"10","key":"4798_CR77","first-page":"1451","volume":"77","author":"E Mochan","year":"2008","unstructured":"Mochan E, Ebell MH (2008) Predicting rheumatoid arthritis risk in adults with undifferentiated arthritis. Am Fam Physician 77(10):1451\u20131453","journal-title":"Am Fam Physician"},{"issue":"5","key":"4798_CR78","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1136\/ard.2010.139527","volume":"70","author":"MG van de Sande","year":"2011","unstructured":"van de Sande MG, de Hair MJ, van der Leij C, Klarenbeek PL, Bos WH, Smith MD et al (2011) Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase. Ann Rheum Dis 70(5):772\u2013777","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"4798_CR79","doi-asserted-by":"publisher","first-page":"e35296","DOI":"10.1371\/journal.pone.0035296","volume":"7","author":"J Sokolove","year":"2012","unstructured":"Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE et al (2012) Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS ONE 7(5):e35296","journal-title":"PLoS ONE"},{"issue":"4","key":"4798_CR80","doi-asserted-by":"publisher","first-page":"205","DOI":"10.4103\/amhsr.amhsr_339_15","volume":"6","author":"K Ghosh","year":"2016","unstructured":"Ghosh K, Chatterjee A, Ghosh S, Chakraborty S, Chattopadhyay P, Bhattacharya A et al (2016) Validation of Leiden score in predicting progression of rheumatoid arthritis in undifferentiated arthritis in Indian population. Ann Med Health Sci Res 6(4):205\u2013210","journal-title":"Ann Med Health Sci Res"},{"issue":"3","key":"4798_CR81","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s12291-019-00844-x","volume":"34","author":"S Dwivedi","year":"2019","unstructured":"Dwivedi S, Purohit P, Sharma P (2019) MicroRNAs and diseases: promising biomarkers for diagnosis and therapeutics. Indian J Clin Biochem 34(3):243\u2013245","journal-title":"Indian J Clin Biochem"},{"issue":"1","key":"4798_CR82","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.ccc.2019.08.008","volume":"36","author":"J Lee","year":"2020","unstructured":"Lee J, Banerjee D (2020) Metabolomics and the microbiome as biomarkers in sepsis. Crit Care Clin 36(1):105\u2013113","journal-title":"Crit Care Clin"}],"container-title":["Rheumatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-021-04798-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00296-021-04798-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-021-04798-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T12:05:36Z","timestamp":1675166736000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00296-021-04798-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":82,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["4798"],"URL":"https:\/\/doi.org\/10.1007\/s00296-021-04798-3","relation":{},"ISSN":["0172-8172","1437-160X"],"issn-type":[{"value":"0172-8172","type":"print"},{"value":"1437-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"12 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"No part of the manuscript is copied or published in whole or in part elsewhere. Its publication has been approved by all co-authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}