Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis
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 (≤250 kcal/day) an...
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MDPI AG
2023-06-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/13/4359 |
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| author | Thomas Häupl Till Sörensen Biljana Smiljanovic Marine Darcy Justus Scheder-Bieschin Nico Steckhan Anika M. Hartmann Daniela A. Koppold Bruno Stuhlmüller Karl Skriner Barbara M. Walewska Berthold Hoppe Marc Bonin Gerd R. Burmester Pascal Schendel Eugen Feist Karsten Liere Martin Meixner Christian Kessler Andreas Grützkau Andreas Michalsen |
| author_facet | Thomas Häupl Till Sörensen Biljana Smiljanovic Marine Darcy Justus Scheder-Bieschin Nico Steckhan Anika M. Hartmann Daniela A. Koppold Bruno Stuhlmüller Karl Skriner Barbara M. Walewska Berthold Hoppe Marc Bonin Gerd R. Burmester Pascal Schendel Eugen Feist Karsten Liere Martin Meixner Christian Kessler Andreas Grützkau Andreas Michalsen |
| author_sort | Thomas Häupl |
| collection | DOAJ |
| description | 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 (≤250 kcal/day) and performed immune monitoring and microbiome sequencing. Patients with metabolic syndrome (<i>n</i> = 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 ∆DAS28 = −1.23; ∆SDAI = −43%) or even achieved remission (DAS28 < 2.6/<i>n</i> = 6; SDAI < 3.3/<i>n</i> = 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. |
| first_indexed | 2024-03-11T01:37:08Z |
| format | Article |
| id | doaj.art-754db97aed0348bfa6dc7f4b10b82490 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T01:37:08Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-754db97aed0348bfa6dc7f4b10b824902023-11-18T16:52:45ZengMDPI AGJournal of Clinical Medicine2077-03832023-06-011213435910.3390/jcm12134359Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid ArthritisThomas Häupl0Till Sörensen1Biljana Smiljanovic2Marine Darcy3Justus Scheder-Bieschin4Nico Steckhan5Anika M. Hartmann6Daniela A. Koppold7Bruno Stuhlmüller8Karl Skriner9Barbara M. Walewska10Berthold Hoppe11Marc Bonin12Gerd R. Burmester13Pascal Schendel14Eugen Feist15Karsten Liere16Martin Meixner17Christian Kessler18Andreas Grützkau19Andreas Michalsen20Department of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyInstitute of Laboratory Medicine, Unfallkrankenhaus Berlin, 12683 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDepartment of Rheumatology and Clinical Immunology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyAmedes Genetics, 10117 Berlin, GermanyAmedes Genetics, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyDeutsches Rheuma-Forschungszentrum, 10117 Berlin, GermanyInstitute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, 10117 Berlin, GermanyRheumatoid 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 (≤250 kcal/day) and performed immune monitoring and microbiome sequencing. Patients with metabolic syndrome (<i>n</i> = 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 ∆DAS28 = −1.23; ∆SDAI = −43%) or even achieved remission (DAS28 < 2.6/<i>n</i> = 6; SDAI < 3.3/<i>n</i> = 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.https://www.mdpi.com/2077-0383/12/13/4359rheumatoid arthritisfastingmonocytescytometric profilingintestinal microbiotamucosal barrier |
| spellingShingle | Thomas Häupl Till Sörensen Biljana Smiljanovic Marine Darcy Justus Scheder-Bieschin Nico Steckhan Anika M. Hartmann Daniela A. Koppold Bruno Stuhlmüller Karl Skriner Barbara M. Walewska Berthold Hoppe Marc Bonin Gerd R. Burmester Pascal Schendel Eugen Feist Karsten Liere Martin Meixner Christian Kessler Andreas Grützkau Andreas Michalsen Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis Journal of Clinical Medicine rheumatoid arthritis fasting monocytes cytometric profiling intestinal microbiota mucosal barrier |
| title | Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis |
| title_full | Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis |
| title_fullStr | Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis |
| title_full_unstemmed | Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis |
| title_short | Intestinal Microbiota Reduction Followed by Fasting Discloses Microbial Triggering of Inflammation in Rheumatoid Arthritis |
| title_sort | intestinal microbiota reduction followed by fasting discloses microbial triggering of inflammation in rheumatoid arthritis |
| topic | rheumatoid arthritis fasting monocytes cytometric profiling intestinal microbiota mucosal barrier |
| url | https://www.mdpi.com/2077-0383/12/13/4359 |
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