{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:13:12Z","timestamp":1783098792140,"version":"3.54.6"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>It has been hypothesized that gut and oral dysbiosis may contribute to the development of primary Sj\u00f6gren\u2019s syndrome (pSS). The aim of this systematic review was to assemble available data regarding the oral and gut microbiota in pSS and to compare them to data from healthy individuals and patients with dry symptoms without a diagnosis of Sj\u00f6gren\u2019s syndrome or lupus disease to identify dysbiosis and discuss the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Using the PRISMA guidelines, we systematically reviewed studies that compared the oral and gut microbiota of Sj\u00f6gren\u2019s patients and controls. The PubMed database and Google Scholar were searched.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two-hundred and eighty-nine studies were found, and 18 studies were included: 13 referred to the oral microbiota, 4 referred to the gut microbiota, and 1 referred to both anatomical sites. The most frequent controls were healthy volunteers and patients with sicca symptoms. The most common analysis method used was 16S-targeted metagenomics. The results were mostly heterogeneous, and the results regarding diversity were not always in accordance. Dysbiosis in pSS was not confirmed, and reduced salivary secretion seems to explain more microbial changes than the underlying disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These heterogeneous results might be explained by the lack of a standardized methodology at each step of the process and highlight the need for guidelines. Our review provides evidence that sicca patients seem to be more relevant than healthy subjects as a control group.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.699011","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T09:23:48Z","timestamp":1627550628000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Healthy Patients Are Not the Best Controls for Microbiome-Based Clinical Studies: Example of Sj\u00f6gren\u2019s Syndrome in a Systematic Review"],"prefix":"10.3389","volume":"12","author":[{"given":"Elise","family":"Doar\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"H\u00e9ry-Arnaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Devauchelle-Pensec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo Carvajal","family":"Alegria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0165","article-title":"The Management of Sj\u00f6gren\u2019s Syndrome","volume":"2","author":"Mavragani","year":"2006","journal-title":"Nat Clin Pract Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2018.03.002","article-title":"Update on Sj\u00f6gren Syndrome and Other Causes of Sicca in Older Adults","volume":"44","author":"Baer","year":"2018","journal-title":"Rheum Dis Clin North Am"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1875-595x.2004.tb00273.x","article-title":"Oral Health Condition and Saliva Flow in Southern Chinese With Sj\u00f6gren\u2019s Syndrome","volume":"54","author":"Leung","year":"2004","journal-title":"Int Dent J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.100","article-title":"Treatment of Primary Sj\u00f6gren Syndrome","volume":"12","author":"Saraux","year":"2016","journal-title":"Nat Rev Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature11234","article-title":"Structure, Function and Diversity of the Healthy Human Microbiome","volume":"486","year":"2012","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-804024-9.00025-2","article-title":"Chapter 25 - Dysbiosis","volume-title":"The Microbiota in Gastrointestinal Pathophysiology","author":"Walker","year":"2017"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12589","article-title":"The Autoimmunity-Oral Microbiome Connection","volume":"23","author":"Nikitakis","year":"2017","journal-title":"Oral Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s12026-012-8311-9","article-title":"Revisiting the Old Link Between Infection and Autoimmune Disease With Commensals and T Helper 17 Cells","volume":"54","author":"Blander","year":"2012","journal-title":"Immunol Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000638","article-title":"Porphyromonas Gingivalis and Rheumatoid Arthritis","volume":"31","author":"Perricone","year":"2019","journal-title":"Curr Opin Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300939","article-title":"Overview of High Throughput Sequencing Technologies to Elucidate Molecular Pathways in Cardiovascular Diseases","volume":"112","author":"Churko","year":"2013","journal-title":"Circ Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/srep23561","article-title":"Altered Mucosal Microbiome Diversity and Disease Severity in Sj\u00f6gren Syndrome","volume":"6","author":"de Paiva","year":"2016","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2535","article-title":"For the PRISMA Group. 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