{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T19:56:16Z","timestamp":1777319776236,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Corona foundation","award":["S199\/10063\/2016"],"award-info":[{"award-number":["S199\/10063\/2016"]}]},{"name":"Corona foundation","award":["(01EC1009A)"],"award-info":[{"award-number":["(01EC1009A)"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["S199\/10063\/2016"],"award-info":[{"award-number":["S199\/10063\/2016"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["(01EC1009A)"],"award-info":[{"award-number":["(01EC1009A)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Rheumatoid arthritis (RA) synovitis is dominated by monocytes\/macrophages with inflammatory patterns resembling microbial stimulation. In search of triggers, we reduced the intestinal microbiome in 20 RA patients (open label study DRKS00014097) by bowel cleansing and 7-day fasting (\u2264250 kcal\/day) and performed immune monitoring and microbiome sequencing. Patients with metabolic syndrome (n = 10) served as a non-inflammatory control group. Scores of disease activity (DAS28\/SDAI) declined within a few days and were improved in 19 of 20 RA patients after breaking the fast (median \u2206DAS28 = \u22121.23; \u2206SDAI = \u221243%) or even achieved remission (DAS28 &lt; 2.6\/n = 6; SDAI &lt; 3.3\/n = 3). Cytometric profiling with 46 different surface markers revealed the most pronounced phenomenon in RA to be an initially increased monocyte turnover, which improved within a few days after microbiota reduction and fasting. Serum levels of IL-6 and zonulin, an indicator of mucosal barrier disruption, decreased significantly. Endogenous cortisol levels increased during fasting but were insufficient to explain the marked improvement. Sequencing of the intestinal microbiota indicated that fasting reduced potentially arthritogenic bacteria and changed the microbial composition to species with broader metabolic capabilities. More eukaryotic, predominantly fungal colonizers were observed in RA, suggesting possible involvement. This study demonstrates a direct link between the intestinal microbiota and RA-specific inflammation that could be etiologically relevant and would support targeted nutritional interventions against gut dysbiosis as a causal therapeutic approach.<\/jats:p>","DOI":"10.3390\/jcm12134359","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T01:15:47Z","timestamp":1688001347000},"page":"4359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3792-9724","authenticated-orcid":false,"given":"Thomas","family":"H\u00e4upl","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Rheumatology, Helios Fachklinik Vogelsang-Gommern GmbH, 39245 Gommern, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Till","family":"S\u00f6rensen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0958-9870","authenticated-orcid":false,"given":"Biljana","family":"Smiljanovic","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marine","family":"Darcy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justus","family":"Scheder-Bieschin","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico","family":"Steckhan","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-9643","authenticated-orcid":false,"given":"Anika M.","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Dermatology, Venereology and Allergology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela A.","family":"Koppold","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Internal and Integrative Medicine, Immanuel Hospital Berlin, 14109 Berlin, Germany"},{"name":"Department of Pediatrics, Division of Oncology and Hematology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3309-4934","authenticated-orcid":false,"given":"Bruno","family":"Stuhlm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Skriner","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara M.","family":"Walewska","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0784-4017","authenticated-orcid":false,"given":"Berthold","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, Unfallkrankenhaus Berlin, 12683 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Bonin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-1131","authenticated-orcid":false,"given":"Gerd R.","family":"Burmester","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Schendel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugen","family":"Feist","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Rheumatology, Helios Fachklinik Vogelsang-Gommern GmbH, 39245 Gommern, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-1449","authenticated-orcid":false,"given":"Karsten","family":"Liere","sequence":"additional","affiliation":[{"name":"Amedes Genetics, 10117 Berlin, Germany"},{"name":"Services in Molecular Biology GmbH, 10115 R\u00fcdersdorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Meixner","sequence":"additional","affiliation":[{"name":"Amedes Genetics, 10117 Berlin, Germany"},{"name":"Services in Molecular Biology GmbH, 10115 R\u00fcdersdorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kessler","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Internal and Integrative Medicine, Immanuel Hospital Berlin, 14109 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Gr\u00fctzkau","sequence":"additional","affiliation":[{"name":"Deutsches Rheuma-Forschungszentrum, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Michalsen","sequence":"additional","affiliation":[{"name":"Institute of Social Medicine, Epidemiology and Health Economics, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t Berlin, 10117 Berlin, Germany"},{"name":"Department of Internal and Integrative Medicine, Immanuel Hospital Berlin, 14109 Berlin, 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