{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:17:49Z","timestamp":1780568269406,"version":"3.54.1"},"reference-count":24,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2021,9,8]]},"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>In the past, the human microbiome has consistently been associated with rheumatoid arthritis (RA) and disease activity. Here, we investigate the antimicrobial activity of disease-modifying antirheumatic drugs (DMARDs) against typical representatives of the oral microflora that have been associated with RA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>DMARDs were screened for antimicrobial activity against bacteria that are associated with the pathogenesis of the disease and\/or frequently isolated from the oral microflora of patients with RA. Screening was done by an agar diffusion assay and minimum inhibitory concentrations (MICs) of antimicrobial active substances were then determined by broth dilution.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Aurothiomalate and sulfasalazine demonstrated broad-spectrum antimicrobial activity, but with MICs ranging from 18 to &gt;280 \u00b5g\/mL and 150 to &gt;600 \u00b5g\/mL, respectively, only at supratherapeutic concentrations. Methotrexate showed antimicrobial activity only against <jats:italic>Fusobacterium nucleatum<\/jats:italic> and <jats:italic>Viridans streptococci<\/jats:italic>. The corresponding MICs were 3.75 to &gt;30 \u00b5g\/mL and 0.5\u201315 \u00b5g\/mL, respectively, thus at least for streptococci, within the therapeutically achievable range. No other DMARD tested showed antimicrobial activity in the agar diffusion screening assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Methotrexate, sulfasalazine and aurothiomalate showed antimicrobial activity against a broad spectrum of RA associated pathogens of the oral microflora. While methotrexate showed relevant antimicrobial activity, and to a more limited extent aurothiomalate, sulfasalazine was active only at far supratherapeutic systemic concentrations. Nevertheless, given the highly species-dependent antimicrobial activity and the multiple ways it can affect the human microbiome, our results suggest a link between antimicrobially active antirheumatic drugs and their potential effect in the treatment of RA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2021-001737","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T13:10:04Z","timestamp":1632921004000},"page":"e001737","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["In vitro evaluation of disease-modifying antirheumatic drugs against rheumatoid arthritis associated pathogens of the oral microflora"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-6655","authenticated-orcid":false,"given":"Manuel","family":"Kussmann","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Obermueller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Spettel","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Clinical Microbiology, Medical University of Vienna, Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2108-0030","authenticated-orcid":false,"given":"Daniel","family":"Aletaha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Wien, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"2025090313494542000_7.3.e001737.1","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1002\/art.40657","article-title":"Microbiota\u2010dependent involvement of Th17 cells in murine models of inflammatory arthritis","volume":"70","author":"Evans-Marin","year":"2018","journal-title":"Arthritis Rheumatol"},{"key":"2025090313494542000_7.3.e001737.2","article-title":"Microbial infection and rheumatoid arthritis","volume":"4","author":"Li","year":"2013","journal-title":"J Clin Cell Immunol"},{"key":"2025090313494542000_7.3.e001737.3","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216681549"},{"key":"2025090313494542000_7.3.e001737.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003627"},{"key":"2025090313494542000_7.3.e001737.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2009.01496.x"},{"key":"2025090313494542000_7.3.e001737.6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3914"},{"key":"2025090313494542000_7.3.e001737.7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1128\/jb.38.5.549-562.1939","article-title":"The relationship between temperature and the Streptococcidal activity of sulfanilamide and sulfapyridine in vitro","volume":"38","author":"White","year":"1939","journal-title":"J Bacteriol"},{"key":"2025090313494542000_7.3.e001737.8","doi-asserted-by":"crossref","DOI":"10.1177\/1759720X19844632","article-title":"The role of microbiome in rheumatoid arthritis treatment","volume":"11","author":"Bodkhe","year":"2019","journal-title":"Ther Adv Musculoskelet Dis"},{"key":"2025090313494542000_7.3.e001737.9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0202278","article-title":"Subgingival microbiome of rheumatoid arthritis patients in relation to their disease status and periodontal health","volume":"13","author":"Beyer","year":"2018","journal-title":"PLoS One"},{"key":"2025090313494542000_7.3.e001737.10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0000516","article-title":"On the action of 5-amino-salicylic acid and sulfapyridine on M. avium including subspecies paratuberculosis","volume":"2","author":"Greenstein","year":"2007","journal-title":"PLoS One"},{"key":"2025090313494542000_7.3.e001737.11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1172\/JCI101112","article-title":"Bactericidal action of sodium sulfapyridine and of a GLUCOSE-SULFAPYRIDINE solution in human blood","volume":"19","author":"Lowell","year":"1940","journal-title":"J Clin Invest"},{"key":"2025090313494542000_7.3.e001737.12","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3934\/microbiol.2018.4.642","article-title":"Drug-microbiota interactions and treatment response: relevance to rheumatoid arthritis","volume":"4","author":"Sayers","year":"2018","journal-title":"AIMS Microbiol"},{"key":"2025090313494542000_7.3.e001737.13","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-62696-3","article-title":"Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae","volume":"10","author":"Elkashif","year":"2020","journal-title":"Sci Rep"},{"key":"2025090313494542000_7.3.e001737.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature25979"},{"key":"2025090313494542000_7.3.e001737.15","article-title":"Oral-Gut microbiota and arthritis: is there an evidence-based axis?","volume":"8","author":"Lorenzo","year":"2019","journal-title":"J Clin Med"},{"key":"2025090313494542000_7.3.e001737.16","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4103\/0976-237X.137959","article-title":"Determination of the antibacterial activity of simvastatin against periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans: an in vitro study","volume":"5","author":"Emani","year":"2014","journal-title":"Contemp Clin Dent"},{"key":"2025090313494542000_7.3.e001737.17","doi-asserted-by":"publisher","DOI":"10.1136\/ard.32.2.128"},{"key":"2025090313494542000_7.3.e001737.18","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.chom.2020.12.008","article-title":"Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation","volume":"29","author":"Nayak","year":"2021","journal-title":"Cell Host Microbe"},{"key":"2025090313494542000_7.3.e001737.19","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02282-13"},{"key":"2025090313494542000_7.3.e001737.20","doi-asserted-by":"publisher","DOI":"10.1038\/nature18849"},{"key":"2025090313494542000_7.3.e001737.21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01202"},{"key":"2025090313494542000_7.3.e001737.22","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.42693","article-title":"Extensive transmission of microbes along the gastrointestinal tract","volume":"8","author":"Schmidt","year":"2019","journal-title":"Elife"},{"key":"2025090313494542000_7.3.e001737.23","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01947-16","article-title":"Phase I clinical trial results of auranofin, a novel antiparasitic agent","volume":"61","author":"Capparelli","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2025090313494542000_7.3.e001737.24","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/cpdd.109","article-title":"The pharmacokinetic effect of coadministration of apremilast and methotrexate in individuals with rheumatoid arthritis and psoriatic arthritis","volume":"3","author":"Liu","year":"2014","journal-title":"Clin Pharmacol Drug Dev"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2021-001737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T20:49:53Z","timestamp":1756932593000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2021-001737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,9,29]]},"published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1136\/rmdopen-2021-001737"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2021-001737","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]}}}