{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:55:22Z","timestamp":1787028922464,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Sj\u00f6gren\u2019s disease (SjD), or primary Sj\u00f6gren\u2019s syndrome (pSS), is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin\u2019s lymphoma in mucosa-associated lymphoid tissue. SjD is one of the autoimmune diseases with the maximum delayed diagnosis due to its insidious onset, heterogeneous clinical features and varied course. It is increasingly recognized that extraglandular manifestations represent a clinical challenge for patients with SjD. The European League Against Rheumatism (EULAR) Sj\u00f6gren\u2019s Syndrome (SS) Disease Activity Index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary Sjogren\u2019s syndrome. It consists of 12 domains: cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, lymphadenopathy and lymphoma, biological. More than a quarter of patients with pSS may have systemic features that are not included in the ESSDAI classification, i.e., various cardiovascular, ophthalmic, ENT, and other systemic or organ involvement that increase the magnitude of the systemic phenotype in the disease. The ESSDAI also excludes the gastrointestinal (GI) tract, and unfortunately, GI manifestations are not routinely assessed. Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal disorders, impairing quality of life and consuming a large volume of medical resources. Recently carried out the Mendelian randomized trial confirmed the causal link between SjD and gastroesophageal reflux disease (GERD) and showed that GERD is a risk factor for SjD. This review aims to provide an overview of the research describing evidenced based links between Sj\u00f6gren\u2019s disease and gastroesophageal reflux disease, with the intention of ensuring that any systemic pathology in Sj\u00f6gren\u2019s disease is properly assessed and that management of the disease is directed towards the patient. A comprehensive literature search was carried out on PubMed, Web of Science, Scopus and the Cochrane Library databases. Two researchers searched for published studies indexed from inception to 1 September 2024 using the keywords \u2018Sj\u00f6gren\u2019s syndrome\u2019 OR \u2018Sj\u00f6gren\u2019s disease\u2019 AND \u2018gastroesophageal reflux disease\u2019 AND \u2018microbiota\u2019 OR microbiota dysbiosis\u2019. We limited our search for scientific articles to human studies, and only included articles in English. Overall, there is a lack of evidence-based studies assessing the association between GERD and Sj\u00f6gren\u2019s disease and the changes in the microbiota associated with GERD in a multidisciplinary setting. Such studies are needed for the future, as this will improve the early diagnosis of Sj\u00f6gren\u2019s disease and the personalized management of the disease.<\/jats:p>","DOI":"10.3390\/medicina60111894","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T13:03:14Z","timestamp":1731934994000},"page":"1894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sj\u00f6gren\u2019s Disease and Gastroesophageal Reflux Disease: What Is Their Evidence-Based Link?"],"prefix":"10.3390","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8412-5227","authenticated-orcid":false,"given":"Diana","family":"Mieliauskait\u0117","sequence":"first","affiliation":[{"name":"Department of Personalised Medicine, State Research Institute Center for Innovative Medicine, Santariskiu st. 5, LT-08405 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilius","family":"Kontenis","sequence":"additional","affiliation":[{"name":"Department of Personalised Medicine, State Research Institute Center for Innovative Medicine, Santariskiu st. 5, LT-08405 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mieliauskaite, D., and Kontenis, V. (2023). Insights into Microbiota in Sj\u00f6gren\u2019s Syndrome. Medicina, 59.","DOI":"10.3390\/medicina59091661"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40744-023-00611-8","article-title":"Epidemiology of Sj\u00f6gren\u2019s: A Systematic Literature Review","volume":"11","author":"Thurtle","year":"2024","journal-title":"Rheumatol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.21037\/gs-20-814","article-title":"Proteomics-based analysis indicating \u03b1-enolase as a potential biomarker in primary Sj\u00f6gren\u2019s syndrome","volume":"9","author":"Wei","year":"2020","journal-title":"Gland Surg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, X.X., Maitiyaer, M., Tan, Q., Huang, W.H., Liu, Y., Liu, Z.P., Wen, Y.Q., Zheng, Y., Chen, X., and Chen, R.L. (2024). Emerging biologic frontiers for Sjogren\u2019s syndrome: Unveiling novel approaches with emphasis on extra glandular pathology. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1377055"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e000022","DOI":"10.1136\/rmdopen-2014-000022","article-title":"EULAR Sj\u00f6gren\u2019s syndrome disease activity index (ESSDAI): A user guide","volume":"1","author":"Seror","year":"2015","journal-title":"RMD Open"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ture, H.Y., Kim, N.R., and Nam, E.J. (2023). EULAR Sjogren\u2019s Syndrome Patient Reported Index (ESSPRI) and Other Patient-Reported Outcomes in the Assessment of Glandular Dysfunction in Primary Sj\u00f6gren\u2019s Syndrome. Life, 13.","DOI":"10.3390\/life13101991"},{"key":"ref_7","first-page":"S97","article-title":"Systemic manifestations of primary Sj\u00f6gren\u2019s syndrome out of the ESSDAI classification: Prevalence and clinical relevance in a large international, multi-ethnic cohort of patients","volume":"37","author":"Retamozo","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mihai, A., Caruntu, C., Jurcut, C., Blajut, F.C., Casian, M., Opris-Belinski, D., Ionescu, R., and Caruntu, A. (2023). The spectrum of extraglandular manifestations in primary Sjogren\u2019s syndrome. J. Pers. Med., 13.","DOI":"10.3390\/jpm13060961"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1515\/rir-2024-0004","article-title":"What can patients tell us in Sj\u00f6gren\u2019s syndrome?","volume":"5","author":"Berry","year":"2024","journal-title":"Rheumatol. Immunol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1590\/s0004-2803.201900000-41","article-title":"Historical perspective of gastroesophageal reflux disease clinical treatment","volume":"56","author":"Zaterka","year":"2019","journal-title":"Arq. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, J., Li, J., Yuan, G., Cao, T., and He, X. (2024). Relationship between Sjogren\u2019s syndrome and gastroesophageal reflux: A bidirectional Mendelian randomization study. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-65512-4"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Parisis, D., Clara Chivasso, C., Jason Perret, J., Soyfoo, M.S., and Delporte, C. (2020). Current State of Knowledge on Primary Sj\u00f6gren\u2019s Syndrome, an Autoimmune Exocrinopathy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072299"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e216","DOI":"10.1016\/S2665-9913(23)00340-5","article-title":"Identification of distinct subgroups of Sj\u00f6gren\u2019s disease by cluster analysis based on clinical and biological manifestations: Data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts","volume":"6","author":"Nguyen","year":"2024","journal-title":"Lancet Rheumatol."},{"key":"ref_14","first-page":"259","article-title":"One year in review 2015: Sj\u00f6gren\u2019s syndrome","volume":"33","author":"Luciano","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_15","first-page":"161","article-title":"One year in review 2016: Sj\u00f6gren\u2019s syndrome","volume":"34","author":"Ferro","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_16","first-page":"179","article-title":"One year in review 2017: Primary Sj\u00f6gren\u2019s syndrome","volume":"35","author":"Ferro","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_17","first-page":"S14","article-title":"One year in review 2018: Sj\u00f6gren\u2019s syndrome","volume":"36","author":"Argyropoulou","year":"2018","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_18","first-page":"S3","article-title":"One year in review 2019: Sj\u00f6gren\u2019s syndrome. One year in review 2019: Sj\u00f6gren\u2019s syndrome","volume":"37","author":"Cafaro","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_19","first-page":"S10","article-title":"One year in review 2020: Comorbidities, diagnosis and treatment of primary Sjogren\u2019s syndrome","volume":"38","author":"Manfre","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.55563\/clinexprheumatol\/eojaol","article-title":"One year in review 2021: Sj\u00f6gren\u2019s syndrome","volume":"39","author":"Cafaro","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_21","first-page":"2211","article-title":"Sj\u00f6gren\u2019s syndrome: One year in review 2022","volume":"40","author":"Chatzis","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41572-021-00287-w","article-title":"Gastro-oesophageal reflux disease","volume":"7","author":"Fass","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/art.30282","article-title":"Antibodies interfering with the type 3 muscarinic receptor pathway inhibit gastrointestinal motility and cholinergic neurotransmission in Sjogren\u2019s syndrome","volume":"63","author":"Park","year":"2011","journal-title":"Arthritis. Rheum."},{"key":"ref_24","first-page":"2343","article-title":"Sj\u00f6gren\u2019s syndrome: One year in review 2023","volume":"41","author":"Longhino","year":"2023","journal-title":"Exp. Rheumatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejim.2016.01.014","article-title":"Increased risk of concurrent gastroesophageal reflux disease among patients with Sj\u00f6gren\u2019s syndrome: A nationwide population-based study","volume":"31","author":"Chang","year":"2016","journal-title":"Eur. J. Int. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S44","DOI":"10.5152\/tjg.2017.12","article-title":"Which diseases are risk factors for developing gastroesophageal reflux disease?","volume":"28","author":"Akyuz","year":"2017","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1007\/s10067-022-06119-w","article-title":"A comprehensive overview of living with Sj\u00f6gren\u2019s: Results of a National Sj\u00f6gren\u2019s Foundation survey","volume":"41","author":"McCoy","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1002\/art.42238","article-title":"Symptom-Based Cluster Analysis Categorizes Sj\u00f6gren\u2019s Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance","volume":"74","author":"McCoy","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Felix Gomez, G.G., Hugenberg, S.T., Zunt, S., Patel, J.S., Wang, M., Rajapuri, A.S., Lembcke, L.R., Rajendran, D., Smith, J.C., and Cherlyan, B. (2023). Characterizing clinical findings of Sjogren\u2019s Disease patients in community practices using matched electronic dental-health record data. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0289335"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1023\/B:DDAS.0000017446.64582.62","article-title":"Esophageal function and Sjogren\u2019s syndrome","volume":"49","author":"Volter","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.molimm.2013.06.004","article-title":"The inhibitory effects of antimuscarinic autoantibodies in the sera of primary Sjogren syndrome patients on the gastrointestinal motility","volume":"56","author":"Parka","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4813795","DOI":"10.1155\/2019\/4813795","article-title":"Sjogren\u2019s Syndrome and TAM Receptors: A Possible Contribution to Disease Onset","volume":"2019","author":"Witas","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1159\/000329381","article-title":"Gastro-oesophageal reflux disease symptoms and tooth wear in patients with Sj\u00f6gren\u2019s syndrome","volume":"45","author":"Nik","year":"2011","journal-title":"Caries Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00296-014-3072-5","article-title":"Sj\u00f6gren\u2019s syndrome: Still not fully understood disease","volume":"35","author":"Maslinska","year":"2015","journal-title":"Rheumatol. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1080\/03009740701607638","article-title":"Dysphagia and dysmotility of the pharynx and oesophagus in patients with primary Sjogren\u2019s syndrome","volume":"36","author":"Mandl","year":"2007","journal-title":"Scand. J. Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s11926-003-0008-6","article-title":"The laryngeal and esophageal manifestations of Sj\u00f6gren\u2019s syndrome","volume":"5","author":"Belafsky","year":"2003","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rihab, B., Lina, E.H., No\u00e9mie, S.T., Jean, S., and Marjolaine, G. (2023). The experience of dry mouth and screening for Sjogren\u2019s syndrome by the dentist: Patient-reported experiences. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-03727-z"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2014.02.004","article-title":"T cell epitope mimicry between Sj\u00f6gren\u2019s syndrome Antigen A (SSA)\/Ro60 and oral, gut, skin and vaginal bacteria","volume":"152","author":"Szymula","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.job.2023.08.005","article-title":"Alterations of The Salivary microbiota in gastroesophageal reflux disease","volume":"65","author":"Qian","year":"2023","journal-title":"J. Oral. Biosci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mazgaeen, L., and Gurung, P. (2020). Recent advances in lipopolysaccharide recognition systems. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020379"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ye, X., Yu, F., Zhou, J., Zhao, C., Wu, J., and Ni, X. (2023). Analysis of the gut microbiota in children with gastroesophageal reflux disease using metagenomics and metabolomics. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1267192"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jaut.2018.10.009","article-title":"Shared gut, but distinct oral microbiota composition in primary Sj\u00f6gren\u2019s syndrome and systemic lupus erythematosus","volume":"97","author":"Harmsen","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/odi.12472","article-title":"The microbiome-systemic diseases connection","volume":"22","author":"Harmsen","year":"2016","journal-title":"Oral. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, K., Wang, S., Chen, Y., Lu, X., Wang, D., Zhang, Y., Pan, W., Zhou, C., and Zou, D. (2024). Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: A genetic correlation and bidirectional Mendelian randomization study. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1327503"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Qin, S., Wang, C., Wang, X., Wu, W., and Liu, C. (2023). Causal association of gastroesophageal reflux disease with obstructive sleep apnea and sleep-related phenotypes: A bidirectional two-sample Mendelian randomization study. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1283286"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"Management of Helicobacter pylori infection-the Mastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2017","journal-title":"Gut"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wang, L., Cao, Z.M., Zhang, L.L., Dai, X.C., Liu, Z.J., Zeng, Y.X., Li, X.Y., Wu, Q.J., and Lv, W. (2022). Helicobacter pylori and autoimmune diseases: Involving multiple systems. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.833424"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chen, J., Zhang, J., Ma, X., Ren, Y., Tang, Y., Zhang, Z., Ye, W., Zhang, Z., Lin, Z., and Wang, L. (2023). Causal relationship between Helicobacter pylori antibodies and gastroesophageal reflux disease (GERD): A Mendelian study. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0294771"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.clim.2019.04.009","article-title":"Sjogren\u2019s syndrome: An update on disease pathogenesis, clinical manifestations and treatment","volume":"203","author":"Vivino","year":"2019","journal-title":"Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lopetuso, L.R., Severgnini, M., Pecere, S., Ponziani, F.R., Boskoski, I., Larghi, A., Quaranta, G., Masucci, L., Ianniro, G., and Camboni, T. (2020). Esophageal microbiome signature in patients with Barrett\u2019s esophagus and esophageal adenocarcinoma. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231789"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.3748\/wjg.v27.i18.2054","article-title":"Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?","volume":"27","author":"Houston","year":"2021","journal-title":"World. J. Gastroenterol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhou, J., Shrestha, P., Qiu, Z., Harman, D.G., Teoh, W.-C., Al-Sohaily, S., Liem, H., Turner, I., and Ho, V. (2020). Distinct microbiota dysbiosis in patients with non-erosive reflux disease and esophageal adenocarcinoma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072162"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Power, D.J., Ho, V., and Zhou, J. (2024). Association between Oral Microbiome and Gastroesophageal Reflux Severity. J. Clin. Med., 13.","DOI":"10.3390\/jcm13154479"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Huang, Y., Kang, Z., He, Y., Qiu, Y., Song, Y., and Liu, W. (2024). Association between gut microbiota and common overlapping gastrointestinal disorders: A bidirectional two-sample Mendelian randomization study. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1343564"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:47Z","timestamp":1760114087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/11\/1894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["medicina60111894"],"URL":"https:\/\/doi.org\/10.3390\/medicina60111894","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]}}}