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Cole LD, Kuhn KA. It Takes a Village: Juvenile Idiopathic Arthritis and the Microbiome. Rheum Dis Clin North Am 2025; 51:233-282. [PMID: 40246440 DOI: 10.1016/j.rdc.2025.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/19/2025]
Abstract
Multiple risk factors for juvenile idiopathic arthritis (JIA) influence the microbiome, and various differences in the oral and fecal microbiome have been described to date in JIA. This review summarizes what is known and discusses potential implications for future research on the microbiome in JIA.
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Affiliation(s)
- Lyndsey D Cole
- Sections of Rheumatology & Infectious Diseases, Department of Pediatrics, University of Colorado Anschutz Medical Campus, 13123 East 16th Avenue, B311, Aurora, CO 80045, USA.
| | - Kristine A Kuhn
- Division of Rheumatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Jena PK, Wakita D, Gomez AC, Carvalho TT, Atici AE, Aubuchon E, Narayanan M, Lee Y, Fishbein MC, Takasato Y, Kurashima Y, Kiyono H, Cani PD, de Vos WM, Underhill DM, Devkota S, Chen S, Shimada K, Crother TR, Arditi M, Rivas MN. Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice. Circ Res 2025; 136:e53-e72. [PMID: 40026151 PMCID: PMC11985309 DOI: 10.1161/circresaha.124.325079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear. METHODS We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed. RESULTS We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation. CONCLUSIONS This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.
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Affiliation(s)
- Prasant K. Jena
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Daiko Wakita
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Angela C. Gomez
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Thacyana T. Carvalho
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Asli E. Atici
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Emily Aubuchon
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Meena Narayanan
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Youngho Lee
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michael C. Fishbein
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, CA, USA
| | - Yoshihiro Takasato
- Department of Allergy, Allergy and Immunology Center, Aichi Children’s Health and Medical Center, Obu, Japan
- Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yosuke Kurashima
- Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Department of Innovative Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Hiroshi Kiyono
- Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Department of Innovative Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan
| | - Patrice D. Cani
- Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), UCLouvain, Université catholique de Louvain, Brussels, Belgium
- WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, WELBIO department, WEL Research Institute, Wavre, Belgium
- Institute of Experimental and Clinical Research (IREC), UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Willem M. de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - David M. Underhill
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- F. Widjaja Inflammatory Bowel Diseases Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Suzanne Devkota
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- F. Widjaja Inflammatory Bowel Diseases Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Human Microbiome Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Shuang Chen
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Kenichi Shimada
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Timothy R. Crother
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Moshe Arditi
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Smidt Heart Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Magali Noval Rivas
- Department of Pediatrics, Division of Infectious Diseases and Immunology, Guerin Children’s at Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Infectious and Immunologic Diseases Research Center (IIDRC), Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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Budzinski L, Sempert T, Lietz L, Maier R, Kang GU, von Stuckrad ASL, Goetzke CC, Roth M, Shah A, Abbas A, Lehman K, Necke K, Bartsch S, Hoffmann U, Mashreghi MF, Biesen R, Kallinich T, Chang HD. Age-stratification reveals age-specific intestinal microbiota signatures in juvenile idiopathic arthritis. Mol Cell Pediatr 2024; 11:12. [PMID: 39653980 PMCID: PMC11628465 DOI: 10.1186/s40348-024-00186-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024] Open
Abstract
OBJECTIVE Juvenile Idiopathic Arthritis (JIA) comprises diverse chronic inflammatory conditions driven by malfunction of the immune system. The intestinal microbiota is considered a crucial environmental factor correlating with chronic inflammatory diseases, and for JIA certain alterations in the microbiota have already been described. METHODS Here, we have characterized intestinal microbiota samples from 54 JIA patients and 38 pediatric healthy controls by conventional 16S rRNA sequencing and by single-cell analysis for phenotypic features by multi-parameter microbiota flow cytometry (mMFC), which complements the population-based taxonomic profiling with the characterization of individual bacterial cells. RESULTS We found age to be a crucial confounder in microbiota analyses of JIA patients. Age stratification revealed specific microbiota alterations neglected by the general comparison of JIA patients and pediatric controls. CONCLUSION Age groups presented distinct taxonomic profiles and microbiota phenotypic signatures which transitioned with age, highlighting changes in the microbiota-immune system interaction with age.
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Affiliation(s)
- Lisa Budzinski
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - Toni Sempert
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Leonie Lietz
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - René Maier
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Gi-Ung Kang
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Anne Sae Lim von Stuckrad
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
| | - Carl Christoph Goetzke
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
| | - Maria Roth
- Department of Rheumatology and Clinical Immunology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Aayushi Shah
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany
| | - Amro Abbas
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Katrin Lehman
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Kathleen Necke
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Stefanie Bartsch
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Ute Hoffmann
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
| | - Mir-Farzin Mashreghi
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
| | - Robert Biesen
- Department of Rheumatology and Clinical Immunology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Tilmann Kallinich
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Campus Virchow, Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), Partner Site Berlin, Berlin, Germany
| | - Hyun-Dong Chang
- German Rheumatology Research Center Berlin - A Leibniz Institute, Charitéplatz 1, Berlin, 10117, Germany.
- Department for Cytometry, Institute of Biotechnology, Technische Universität Berlin, Berlin, Germany.
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Bellando-Randone S, Russo E, Di Gloria L, Lepri G, Baldi S, Fioretto BS, Romano E, Ghezzi G, Bertorello S, El Aoufy K, Rosa I, Pallecchi M, Bruni C, Cei F, Nannini G, Niccolai E, Orlandi M, Bandini G, Guiducci S, Bartolucci GL, Ramazzotti M, Manetti M, Matucci-Cerinic M, Amedei A. Gut microbiota in very early systemic sclerosis: the first case-control taxonomic and functional characterisation highlighting an altered butyric acid profile. RMD Open 2024; 10:e004647. [PMID: 39557490 PMCID: PMC11574430 DOI: 10.1136/rmdopen-2024-004647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/23/2024] [Indexed: 11/20/2024] Open
Abstract
OBJECTIVES In systemic sclerosis (SSc), gastrointestinal involvement is one of the earliest events. We compared the gut microbiota (GM), its short-chain fatty acids (SCFAs) and host-derived free fatty acids (FFAs) in patients with very early diagnosis of SSc (VEDOSS) and definite SSc. METHODS Stool samples of 26 patients with SSc, 18 patients with VEDOSS and 20 healthy controls (HC) were collected. The GM was assessed through 16S rRNA sequencing, while SCFAs and FFAs were assessed by gas chromatography-mass spectrometry. RESULTS In patients with VEDOSS, an increase in Bacteroidales and Oscillospirales orders and a decrease in Bacilli class, Blautia, Romboutsia, Streptococcus and Turicibacter genera was detected in comparison with HC. In patients with SSc, an elevated number of Acidaminococcaceae and Sutterellaceae families, along with a decrease of the Peptostreptococcaceae family and Anaerostipes, Blautia, Romboutsia and Turicibacter genera was found in comparison with HC. Patients with SSc and VEDOSS had a significantly lower butyrate and higher acetate with respect to HC. In VEDOSS, an increase in Oscillospiraceae family and Anaerostipes genus, and a decrease in Alphaproteobacteria class, and Lactobacillales order was identified with respect to SSc. Moreover, patients with VEDOSS exhibited higher acetate and lower valerate compared with definite SSc. CONCLUSION A GM dysbiosis with depletion of beneficial anti-inflammatory bacteria (especially butyrate-producing) and a significant decrease in faecal butyrate was identified in patients with VEDOSS. This early GM imbalance may foster the growth of inflammatory microbes, worsening intestinal dysbiosis and inflammation in early SSc stages. The potential butyrate administration in early disease phases might be considered as a novel therapeutic approach to mitigate gastrointestinal discomfort and progression preserving patient's quality of life.
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Affiliation(s)
- Silvia Bellando-Randone
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
- Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy
| | - Edda Russo
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Leandro Di Gloria
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Gemma Lepri
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
- Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy
| | - Simone Baldi
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Bianca Saveria Fioretto
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
| | - Eloisa Romano
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Giulio Ghezzi
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
| | - Sara Bertorello
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Khadija El Aoufy
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Irene Rosa
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
- Department of Experimental and Clinical Medicine, Imaging Platform, University of Florence, Florence, Italy
| | - Marco Pallecchi
- Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
| | - Cosimo Bruni
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
- Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
| | - Francesco Cei
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Giulia Nannini
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Elena Niccolai
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Martina Orlandi
- Department of Medical and Surgical Sciences for Children, University of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Bandini
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
| | - Serena Guiducci
- Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Florence, Italy
- Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy
| | - Gian Luca Bartolucci
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Florence, Italy
| | - Matteo Ramazzotti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Mirko Manetti
- Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy
- Department of Experimental and Clinical Medicine, Imaging Platform, University of Florence, Florence, Italy
| | - Marco Matucci-Cerinic
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
- Vita Salute San Raffaele University, Milan, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, Florence, Italy
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Zhang L, Yang Z, Zhang L, Wei Y, Wan L. Causal effect of gut microbiota on juvenile idiopathic arthritis: A two-sample Mendelian a randomization study. J Cell Mol Med 2024; 28:e70183. [PMID: 39473264 PMCID: PMC11522359 DOI: 10.1111/jcmm.70183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 09/03/2024] [Accepted: 10/19/2024] [Indexed: 11/02/2024] Open
Abstract
There is increasing evidence of a significant association between the gut microbiome and juvenile idiopathic arthritis (JIA). However, whether this association is causal remains to be determined. This study was a two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data to investigate the causal relationship between the gut microbiome and JIA. We used summary data on gut flora and JIA obtained from genome-wide association studies (GWAS) from MiBioGen and NHGRI-EBI, using inverse variance weighting as the main method to analyse causality in the TSMR causality analysis. To check the stability of the TSMR results, we performed several sensitivity analyses and assessed the presence of reverse causality through a reverse TSMR analysis. We calculated the degree of sample overlap where applicable. The current TSMR analyses identified four bacterial taxa associated with JIA. Specifically, two bacteria, Catenibacterium (p = 2 × 10-2) and Holdemania (p = 4 × 10-2), were negatively associated with the risk of developing JIA, suggesting a protective effect, while Olsenella (p = 1 × 10-2) and Rikenellaceae (RC9gutgroup) (p = 1 × 10-2) were positively associated with the risk of JIA, suggesting that these two bacteria may be risk factors for JIA. However, the results for Catenibacterium and Holdemania should be interpreted with caution due to instability observed in 'leave-one-out' sensitivity analyses. Reverse TSMR analyses found no evidence of reverse causality between JIA and gut flora. Our confirmation of a causal relationship between gut flora and JIA provides an innovative perspective for the study of JIA: targeting and modulating dysregulation of specific bacterial taxa to prevent and treat JIA.
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Affiliation(s)
- Lian Zhang
- Shenzhen Children's HospitalShenzhenChina
| | - Zhihua Yang
- Department of Internal Medicine V Hematology Oncology RheumatologyHeidelberg University HospitalHeidelbergGermany
| | - LuLu Zhang
- Shenzhen Children's HospitalShenzhenChina
| | - Yanwen Wei
- Shenzhen Hospital of Integrated Traditional Chinese and Wsestern MedicineShenzhenChina
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6
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Hong JB, Chen YX, Su ZY, Chen XY, Lai YN, Yang JH. Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study. Front Immunol 2024; 15:1356414. [PMID: 39114654 PMCID: PMC11303189 DOI: 10.3389/fimmu.2024.1356414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 07/04/2024] [Indexed: 08/10/2024] Open
Abstract
Background The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (β: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.
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Affiliation(s)
- Jun-bin Hong
- Department of Pediatrics, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yue-xuan Chen
- Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, China
| | - Zhi-ying Su
- Department of Pediatrics, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xin-ying Chen
- Department of Pediatrics, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yan-ni Lai
- School of Medicine and Health, Shunde Polytechnic, Foshan, China
| | - Jing-hua Yang
- Department of Pediatrics, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
- Xiaorong Luo’s National Renowned Expert Inheritance Studio, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
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7
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Jena PK, Wakita D, Gomez AC, Carvalho TT, Atici AE, Narayanan M, Lee Y, Fishbein MC, Cani PD, de Vos WM, Underhill DM, Devkota S, Chen S, Shimada K, Crother TR, Arditi M, Rivas MN. The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.28.596258. [PMID: 38853964 PMCID: PMC11160596 DOI: 10.1101/2024.05.28.596258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2024]
Abstract
Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from A. muciniphila , also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function. IN BRIEF It remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jena et al. observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reduced A. muciniphila and F. prausnitzii . Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein of A. muciniphila , was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function. HIGHLIGHTS Absence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis. Supplementation of B. wadsworthia and B. fragilis promotes murine KD vasculitis. Decreased abundances of F. prausnitzii and A. muciniphila are associated with the development of cardiovascular lesions in mice. Supplementation with either live or pasteurized A. muciniphila and F. prausnitzii, or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function.
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Tang J, Mo S, Fan L, Fu S, Liu X. Causal association of gut microbiota on spondyloarthritis and its subtypes: a Mendelian randomization analysis. Front Immunol 2024; 15:1284466. [PMID: 38390322 PMCID: PMC10883304 DOI: 10.3389/fimmu.2024.1284466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/18/2024] [Indexed: 02/24/2024] Open
Abstract
Background Despite establishing an association between gut microbiota and spondyloarthritis (SpA) subtypes, the causal relationship between them remains unclear. Methods Gut microbiota data were obtained from the MiBioGen collaboration, and SpA genome-wide association study (GWAS) summary data were obtained from the FinnGen collaboration. We conducted a two-sample Mendelian randomization (MR) analysis using the inverse-variance-weighted method supplemented with four additional MR methods (MR-Egger, weighted median, simple mode, and weighted mode). Pleiotropy and heterogeneity were also assessed. Reverse MR analysis was used to detect reverse causal relationships. Results We identified 23 causal links between specific gut microbiota taxa and SpA levels. Of these, 22 displayed nominal causal associations, and only one demonstrated a robust causal connection. Actinobacteria id.419 increased the risk of ankylosing spondylitis (AS) (odds ratio (OR) = 1.86 (95% confidence interval (CI): 1.29-2.69); p = 8.63E-04). The family Rikenellaceae id.967 was associated with a reduced risk of both AS (OR = 0.66 (95% CI: 0.47-0.93); p = 1.81E-02) and psoriatic arthritis (OR = 0.70 (95% CI: 0.50-0.97); p = 3.00E-02). Bacillales id.1674 increased the risk of AS (OR = 1.23 (95% CI: 1.00-1.51); p = 4.94E-02) and decreased the risk of enteropathic arthritis (OR = 0.56 (95% CI: 0.35-0.88); p = 1.14E-02). Directional pleiotropy, or heterogeneity, was not observed. No reverse causal associations were observed between the diseases and the gut microbiota. Conclusion Our MR analysis suggested a genetic-level causal relationship between specific gut microbiota and SpA, providing insights into the underlying mechanisms behind SpA development mediated by gut microbiota.
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Affiliation(s)
- Jun Tang
- Experimental Teaching Management Center, Chongqing Medical University, Chongqing, China
| | - Shiyan Mo
- Department of Rheumatology and Immunology, Hainan Hospital of Chinese People's Liberation Army of China (PLA) General Hospital, Sanya, Hainan, China
| | - Lina Fan
- Department of Rheumatology and Immunology, Hainan Hospital of Chinese People's Liberation Army of China (PLA) General Hospital, Sanya, Hainan, China
| | - Shihui Fu
- Department of Cardiovascular, Hainan Hospital of Chinese People’s Liberation Army of China (PLA) General Hospital, Sanya, Hainan, China
| | - Xiaofei Liu
- Department of Rheumatology and Immunology, Hainan Hospital of Chinese People's Liberation Army of China (PLA) General Hospital, Sanya, Hainan, China
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9
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Wang H, Bi H, Yang M, Wang X, Song C, Yang W, Wang Y, Xie D, Li H, Zhou Z. Intestinal flora altered and correlated with interleukin-2/4 in patients with primary immune thrombocytopenia. Hematology 2023; 28:2277501. [PMID: 37921501 DOI: 10.1080/16078454.2023.2277501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 10/25/2023] [Indexed: 11/04/2023] Open
Abstract
BACKGROUND Little is known about the changes and mechanisms of intestinal flora in primary immune thrombocytopenia (ITP) patients. AIM To explore the structural and functional differences of intestinal flora between ITP patients and healthy controls, and clarify the correlation between intestinal flora and Th1/Th2 imbalance. METHODS Feces from ITP patients and healthy controls were studied by 16S rRNA and metagenomic techniques at phylum, genus, species or functional levels. Blood samples were collected for the detection of interleukin -2 (IL-2) and IL-4 concentrations. RESULTS The following changes in ITP patients were found: a decrease of Bacteroidetes phylum, an increase of Proteobacteria phylum and alterations of ten genera and 1045 species. IL-2 and IL-4 were significantly correlated with six and five genera, respectively. Species of C. freundii, C. rodentium, and C. youngae were negatively correlated with bleeding scores, and S. infantis was positively related to platelet counts. Functionally, the intestinal flora of ITP patients changed mainly in terms of motility, chemotaxis, membrane transport, and metabolism. CONCLUSION The mechanism underlying functional and structural changes of intestinal flora in ITP patients may be related to inflammation and immunity, providing possibilities of probiotics or fecal transplants for ITP.
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Affiliation(s)
- Honghui Wang
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Hui Bi
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Muran Yang
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Xiuli Wang
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Chuanju Song
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Wen Yang
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Yacan Wang
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Dongmei Xie
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Huiting Li
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
| | - Zeping Zhou
- Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China
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Kindgren E, Ahrens AP, Triplett EW, Ludvigsson J. Infant gut microbiota and environment associate with juvenile idiopathic arthritis many years prior to disease onset, especially in genetically vulnerable children. EBioMedicine 2023; 93:104654. [PMID: 37329576 PMCID: PMC10279551 DOI: 10.1016/j.ebiom.2023.104654] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 05/13/2023] [Accepted: 05/31/2023] [Indexed: 06/19/2023] Open
Abstract
BACKGROUND The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a prospective birth cohort to assess disease risk. METHODS Data was collected from the All Babies in Southeast Sweden (ABIS) population-based cohort (n = 17,055), 111 of whom later acquired JIA (ABISJIA). Stool samples were collected at one year of age for 10.4%. To determine disease association, 16S rRNA gene sequences were analyzed, with and without confound adjustment. Genetic and environmental risks were assessed. FINDINGS ABISJIA had higher abundance of Acidaminococcales, Prevotella 9, and Veillonella parvula and lower abundance of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis, and Akkermansia muciniphila (q's < 0.05). Parabacteroides distasonis greatly increased the odds of later contracting JIA (OR = 6.7; 1.81-24.84, p = 0.0045). Shorter breastfeeding duration and increased antibiotic exposure compounded risk in a dose-dependent manner, especially in those with genetic predisposition. INTERPRETATION Microbial dysregulation in infancy may trigger or accelerate JIA development. Environmental risk factors have a stronger impact on genetically predisposed children. This study is the first to implicate microbial dysregulation in JIA at such an early age, with many bacterial taxa associated with risk factors. These findings provide opportunities for intervention or early screening and offer new insights into JIA pathogenesis. FUNDING Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping.
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Affiliation(s)
- Erik Kindgren
- Department of Pediatrics, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden; Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Angelica P Ahrens
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611-0700, USA
| | - Eric W Triplett
- Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611-0700, USA.
| | - Johnny Ludvigsson
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Crown Princess Victoria's Children's Hospital, Region Östergötland, Linköping, SE 58185, Sweden
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11
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Boix-Amorós A, Badri MH, Manasson J, Blank RB, Haberman RH, Neimann AL, Girija PV, Jimenez Hernandez A, Heguy A, Koralov SB, Bonneau R, Clemente JC, Scher JU. Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin. Ann Rheum Dis 2023; 82:507-514. [PMID: 36600182 PMCID: PMC11131958 DOI: 10.1136/ard-2022-223389] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 12/01/2022] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA). METHODS Skin swabs were collected from upper and lower extremities of healthy individuals and patients with PsO and PsA. Psoriatic patients contributed both lesional (L) and contralateral non-lesional (NL) samples. Microbiota were analysed using 16S rRNA sequencing. RESULTS Compared with healthy skin, alpha diversity in psoriatic NL and L skin was significantly reduced (p<0.05) and samples clustered separately in plots of beta diversity (p<0.05). Kocuria and Cutibacterium were enriched in healthy subjects, while Staphylococcus was enriched in psoriatic disease. Microbe-microbe association networks revealed a higher degree of similarity between psoriatic NL and L skin compared with healthy skin despite the absence of clinically evident inflammation. Moreover, the relative abundance of Corynebacterium was higher in NL PsA samples compared with NL PsO samples (p<0.05), potentially serving as a biomarker for disease progression. CONCLUSIONS These findings show differences in diversity, bacterial composition and microbe-microbe interactions between healthy and psoriatic skin, both L and NL. We further identified bacterial biomarkers that differentiate disease phenotypes, which could potentially aid in predicting the transition from PsO to PsA.
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Affiliation(s)
- Alba Boix-Amorós
- Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Michelle H Badri
- Department of Biology, New York University, New York, New York, USA
| | - Julia Manasson
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
| | - Rebecca B Blank
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
| | - Rebecca H Haberman
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
| | - Andrea L Neimann
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York, USA
| | - Parvathy V Girija
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
| | - Anthony Jimenez Hernandez
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
| | - Adriana Heguy
- NYU Langone Health Genome Technology Center, Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA
- Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA
| | - Sergei B Koralov
- Department of Pathology, New York University Grossman School of Medicine, New York, New York, USA
| | - Richard Bonneau
- Department of Biology, New York University, New York, New York, USA
- Center for Computational Biology, Flatiron Institute, Simons Foundation, New York, New York, USA
| | - Jose C Clemente
- Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jose U Scher
- Division of Rheumatology, Department of Medicine and Psoriatic Arthritis Center, New York University Grossman School of Medicine, New York, New York, USA
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12
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Jeyaraman M, Nallakumarasamy A, Jain VK. Gut Microbiome - Should we treat the gut and not the bones? J Clin Orthop Trauma 2023; 39:102149. [PMID: 37009327 PMCID: PMC10064415 DOI: 10.1016/j.jcot.2023.102149] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 03/18/2023] [Indexed: 04/03/2023] Open
Abstract
Gut microbiome (GM) forms an integral part of homeostasis of an individual. Due to the recent development of metagenomics, the plausibility of sequencing GM and its therapeutic ability for various diseases has been explored. Dysbiosis or disequilibrium or pertubations of GM leads to disruption of intercommunication signaling among gut-bone axis, gut-bone-brain axis, and gut-disc axis resulting in the progression of various chronic diseases. The therapeutic interventions to restore the GM like prebiotics and probiotics, bacteriophage therapy, fecal microbiota transplantation, and physical biomodulation have been identified. This review throw the lime light on the effect of gut dysbiosis in musculoskeletal diseases.
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Affiliation(s)
- Madhan Jeyaraman
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai, 600056, Tamil Nadu, India
| | - Arulkumar Nallakumarasamy
- Department of Orthopaedics, All India Institute of Medical Sciences, Bhubaneswar, 751019, Odisha, India
| | - Vijay Kumar Jain
- Department of Orthopaedics, Atal Bihari Vajpayee Institute of Medical Sciences, Dr Ram Manohar Lohia Hospital, New Delhi, 110001, India
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13
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Li C, Zhang Y, Yan Q, Guo R, Chen C, Li S, Zhang Y, Meng J, Ma J, You W, Wu Z, Sun W. Alterations in the gut virome in patients with ankylosing spondylitis. Front Immunol 2023; 14:1154380. [PMID: 37063855 PMCID: PMC10098016 DOI: 10.3389/fimmu.2023.1154380] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 03/20/2023] [Indexed: 04/03/2023] Open
Abstract
IntroductionAnkylosing spondylitis (AS), a chronic autoimmune disease, has been linked to the gut bacteriome.MethodsTo investigate the characteristics of the gut virome in AS, we profiled the gut viral community of 193 AS patients and 59 healthy subjects based on a metagenome-wide analysis of fecal metagenomes from two publicly available datasets.ResultsAS patients revealed a significant decrease in gut viral richness and a considerable alteration of the overall viral structure. At the family level, AS patients had an increased abundance of Gratiaviridae and Quimbyviridae and a decreased abundance of Drexlerviridae and Schitoviridae. We identified 1,004 differentially abundant viral operational taxonomic units (vOTUs) between patients and controls, including a higher proportion of AS-enriched Myoviridae viruses and control-enriched Siphoviridae viruses. Moreover, the AS-enriched vOTUs were more likely to infect bacteria such as Flavonifractor, Achromobacter, and Eggerthellaceae, whereas the control-enriched vOTUs were more likely to be Blautia, Ruminococcus, Collinsella, Prevotella, and Faecalibacterium bacteriophages. Additionally, some viral functional orthologs differed significantly in frequency between the AS-enriched and control-enriched vOTUs, suggesting the functional role of these AS-associated viruses. Moreover, we trained classification models based on gut viral signatures to discriminate AS patients from healthy controls, with an optimal area under the receiver operator characteristic curve (AUC) up to 0.936, suggesting the clinical potential of the gut virome for diagnosing AS.DiscussionThis work provides novel insight into the AS gut virome, and the findings may guide future mechanistic and therapeutic studies for other autoimmune diseases.
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Affiliation(s)
- Chen Li
- Department of Rheumatology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yan Zhang
- Department of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Qiulong Yan
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | | | - Changming Chen
- Department of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | | | - Yue Zhang
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | | | - Jie Ma
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wei You
- Beijing Key Laboratory of Acupuncture Neuromodulation, Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Zhisong Wu
- Department of Intensive Care Medicine, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Wen Sun
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, China
- Beijing Key Laboratory of Health Cultivation, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Wen Sun,
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14
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González-Chávez SA, Salas-Leiva JS, Salas-Leiva DE, López-Loeza SM, Sausameda-García J, Orrantia-Borunda E, Burgos-Vargas R, Alvarado-Jáquez MF, Torres-Quintana M, Cuevas-Martínez R, Chaparro-Barrera E, Marín-Terrazas C, Espino-Solís GP, Romero-López JP, Bernal-Alferes BDJ, Pacheco-Tena C. Levofloxacin induces differential effects in the transcriptome between the gut, peripheral and axial joints in the Spondyloarthritis DBA/1 mice: Improvement of intestinal dysbiosis and the overall inflammatory process. PLoS One 2023; 18:e0281265. [PMID: 36730179 PMCID: PMC9894406 DOI: 10.1371/journal.pone.0281265] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 01/18/2023] [Indexed: 02/03/2023] Open
Abstract
To analyze the effect of levofloxacin-induced intestinal microbiota modifications on intestinal, joint, and systemic inflammation in the DBA/1 mice with spontaneous arthritis. The study included two groups of mice, one of which received levofloxacin. The composition and structure of the microbiota were determined in the mice's stool using 16S rRNA sequencing; the differential taxa and metabolic pathway between mice treated with levofloxacin and control mice were also defied. The effect of levofloxacin was evaluated in the intestines, hind paws, and spines of mice through DNA microarray transcriptome and histopathological analyses; systemic inflammation was measured by flow cytometry. Levofloxacin decreased the pro-inflammatory bacteria, including Prevotellaceae, Odoribacter, and Blautia, and increased the anti-inflammatory Muribaculaceae in mice's stool. Histological analysis confirmed the intestinal inflammation in control mice, while in levofloxacin-treated mice, inflammation was reduced; in the hind paws and spines, levofloxacin also decreased the inflammation. Microarray showed the downregulation of genes and signaling pathways relevant in spondyloarthritis, including several cytokines and chemokines. Levofloxacin-treated mice showed differential transcriptomic profiles between peripheral and axial joints and intestines. Levofloxacin decreased the expression of TNF-α, IL-23a, and JAK3 in the three tissues, but IL-17 behaved differently in the intestine and the joints. Serum TNF-α was also reduced in levofloxacin-treated mice. Our results suggest that the microbiota modification aimed at reducing pro-inflammatory and increasing anti-inflammatory bacteria could potentially be a coadjuvant in treating inflammatory arthropathies.
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Affiliation(s)
- Susana Aideé González-Chávez
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Joan S. Salas-Leiva
- Departamento de Medio Ambiente y Energía, CONACyT-Centro de Investigación en Materiales Avanzados, Chihuahua, México
| | - Dayana E. Salas-Leiva
- Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
- Department of Biochemistry and Molecular Biology, Institute for Comparative Genomics (ICG), Dalhousie University, Halifax, NS, Canada
| | - Salma Marcela López-Loeza
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Jasanai Sausameda-García
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Erasmo Orrantia-Borunda
- Departamento de Medio Ambiente y Energía, CONACyT-Centro de Investigación en Materiales Avanzados, Chihuahua, México
| | - Rubén Burgos-Vargas
- Department of Rheumatology, Hospital General de México, "Dr. Eduardo Liceaga", Ciudad de México, México
| | | | - Mayra Torres-Quintana
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Rubén Cuevas-Martínez
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Eduardo Chaparro-Barrera
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Carlos Marín-Terrazas
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
| | - Gerardo Pável Espino-Solís
- Translational Research Laboratory and National Laboratory of Flow Cytometry, Autonomous University of Chihuahua, Circuito Universitario, Campus II, Chihuahua, Mexico
| | - José Pablo Romero-López
- Laboratorio de Inmunología Clínica 1, Instituto Politécnico Nacional de México, Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Ciudad de México, México
| | - Brian de Jesús Bernal-Alferes
- Laboratorio de Inmunología Clínica 1, Instituto Politécnico Nacional de México, Posgrado en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Ciudad de México, México
| | - César Pacheco-Tena
- Facultad de Medicina y Ciencias Biomédicas, Laboratorio PABIOM, Universidad Autónoma de Chihuahua, Chihuahua, México
- * E-mail:
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Porosyuk MV, Klementiev DD, Hodov NA, Gumenyuk LN, Esatova ES, Sereda EV, Chetveruhina-Malova KS, Sarchuk EV, Ivanov SV. Gut microbiota alterations in patients with juvenile idiopathic arthritis. BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY 2022. [DOI: 10.24075/brsmu.2022.060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.
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Affiliation(s)
- MV Porosyuk
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - DD Klementiev
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - NA Hodov
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - LN Gumenyuk
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - ES Esatova
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - EV Sereda
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | | | - EV Sarchuk
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
| | - SV Ivanov
- Georgievsky Medical Academy, Vernadsky Crimean Federal University, Simferopol, Russia
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Zeng L, Deng Y, He Q, Yang K, Li J, Xiang W, Liu H, Zhu X, Chen H. Safety and efficacy of probiotic supplementation in 8 types of inflammatory arthritis: A systematic review and meta-analysis of 34 randomized controlled trials. Front Immunol 2022; 13:961325. [PMID: 36217542 PMCID: PMC9547048 DOI: 10.3389/fimmu.2022.961325] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To evaluate Safety and efficacy of probiotic supplementation in inflammatory arthritis. Methods The literature on the treatment of inflammatory arthritis with probiotics has been collected in databases such as CNKI, Pubmed, Cochrane library, Embase, etc. The search time is for them to build the database until May 2022. The included literatures are randomized controlled trials (RCTs) of probiotics in the treatment of hyperuricemia and gout. The Cochrane risk assessment tool was used for quality evaluation, and the Rev Man5.3 software was used for meta-analysis. Results A total of 37 records were finally included, involving 34 RCTs and 8 types of autoimmune disease (Hyperuricemia and gout, Inflammatory bowel disease arthritis, juvenile idiopathic arthritis [JIA], Osteoarthritis [OA], Osteoporosis and Osteopenia, Psoriasis, rheumatoid arthritis (RA), Spondyloarthritis). RA involved 10 RCTs (632 participants) whose results showed that probiotic intervention reduced CRP. Psoriasis involved 4 RCTs (214 participants) whose results showed that probiotic intervention could reduce PASI scores. Spondyloarthritis involved 2 RCTs (197 participants) whose results showed that probiotic intervention improved symptoms in patients. Osteoporosis and Ostepenia involving 10 RCTs (1156 participants) showed that probiotic intervention improved bone mineral density in patients. Hyperuricemia and gout involving 4 RCTs (294 participants) showed that probiotic intervention improved serum uric acid in patients. OA involving 1 RCTs (433 participants) showed that probiotic intervention improved symptoms in patients. JIA involving 2 RCTs (72 participants) showed that probiotic intervention improved symptoms in patients. Inflammatory bowel disease arthritis involving 1 RCTs (120 participants) showed that probiotic intervention improved symptoms in patients. All of the above RCTs showed that probiotics did not increase the incidence of adverse events. Conclusion Probiotic supplements may improve Hyperuricemia and gout, Inflammatory bowel disease arthritis, JIA, OA, Osteoporosis and Osteopenia, Psoriasis, RA, Spondyloarthritis. However, more randomized controlled trials are needed in the future to determine the efficacy and optimal dosing design of probiotics. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021286425, identifier CRD42021286425.
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Affiliation(s)
- Liuting Zeng
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Ying Deng
- People’s Hospital of Ningxiang City, Ningxiang, China
| | - Qi He
- People’s Hospital of Ningxiang City, Ningxiang, China
| | - Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Jun Li
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | - Wang Xiang
- The First People's Hospital of Changde City, Changde, China
| | - Huiping Liu
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, China
| | | | - Hua Chen
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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Berntson L, Öman A, Engstrand L, Dicksved J. A Pilot Study Investigating Faecal Microbiota After Two Dietary Interventions in Children with Juvenile Idiopathic Arthritis. Curr Microbiol 2022; 79:215. [PMID: 35672613 PMCID: PMC9174309 DOI: 10.1007/s00284-022-02899-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 05/09/2022] [Indexed: 11/21/2022]
Abstract
There is evidence for an impact of the gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN) and the specific carbohydrate diet (SCD) have been demonstrated as effective anti-inflammatory treatments for children with Crohn’s disease. We have previously shown an anti-inflammatory effect from these nutritional treatments in children with juvenile idiopathic arthritis (JIA). The aim of this study was to investigate if improved clinical symptoms after EEN or SCD treatment in children with JIA could be linked to changes in faecal microbiota. We included sixteen patients with JIA (age 7–17 years), six for treatment with EEN and ten with SCD. EEN was given for 3–5 weeks and SCD for 4–5 weeks, with clinical and laboratory status assessed before and after treatment. Faecal samples were analysed for microbiota diversity and composition using 16S rRNA gene sequencing. Analyses of the faecal microbiota showed an effect on the overall composition with both interventions; the most striking result was a decreased relative abundance of the genus Faecalibacterium from EEN and of Bifidobacterium from SCD. The α-diversity decreased significantly from SCD (P = 0.04), but not from EEN (P = 0.22). Despite the study cohorts being small, both EEN and SCD were shown to impact the faecal microbiota. Future larger studies with a focus on metagenomics or metabolomics could possibly reveal a link and clarify the clinical effects of those nutritional regimens.
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[Changes of intestinal flora in children with acute lymphoblastic leukemia before and after chemotherapy]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2022; 24:550-560. [PMID: 35644196 PMCID: PMC9154360 DOI: 10.7499/j.issn.1008-8830.2110045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVES To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. METHODS Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. RESULTS The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). CONCLUSIONS The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.
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Wan Y, Yang L, Jiang S, Qian D, Duan J. Excessive Apoptosis in Ulcerative Colitis: Crosstalk Between Apoptosis, ROS, ER Stress, and Intestinal Homeostasis. Inflamm Bowel Dis 2022; 28:639-648. [PMID: 34871402 DOI: 10.1093/ibd/izab277] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium and destruction of the intestinal homeostasis, which has caused a huge social and economic burden on the health system all over the world. Its pathogenesis is multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, and dysregulated immune response. Thus far, although immune cells have become the focus of most research, it is increasingly clear that intestinal epithelial cells play an important role in the pathogenesis and progression of UC. Notably, apoptosis is a vital catabolic process in cells, which is crucial to maintain the stability of intestinal environment and regulate intestinal ecology. In this review, the mechanism of apoptosis induced by reactive oxygen species and endoplasmic reticulum stress, as well as excessive apoptosis in intestinal epithelial dysfunction and gut microbiology imbalance are systematically and comprehensively summarized. Further understanding the role of apoptosis in the pathogenesis of UC may provide a novel strategy for its therapy in clinical practices and the development of new drugs.
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Affiliation(s)
- Yue Wan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Lei Yang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Shu Jiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, PR China
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20
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Hursitoglu M, Isıksacan N, Erismis B, Karandere F, Kural A, Kumbasar AB, Kart Yasar K. In-vitro cytokine production and nasopharyngeal microbiota composition in the early stage of COVID-19 infection. Cytokine 2022; 149:155757. [PMID: 34763156 PMCID: PMC8570934 DOI: 10.1016/j.cyto.2021.155757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/26/2021] [Accepted: 10/26/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND To determine and compare nasopharyngeal microbiota (NM) composition, in vitro basal (Nil tube), provoked (Mitogen tube) production of cytokines at the early stage of COVID-19. METHODS This cross-sectional study included 4 age and sex-matched study groups; group 1 (recovered COVID-19) (n = 26), group 2 (mild COVID-19) (n = 24), group 3 (severe COVID-19) (n = 25), and group 4 (healthy controls) (n = 25). The study parameters obtained from the COVID-19 (group 2, and 3) at the early phase of hospital admission. RESULTS The results from the reaserch deoicted that the Mean ± SD age was 53.09 ± 14.51 years. Some of the in vitro cytokines production was significantly different between the study groups. Some of the findinggs on cytokines depicted a significant differences between study groups were interleukin (IL)-1β Nil, IL-1β Mitogen, and their subtraction (i.e Mitogen-Nil). Regarding IL-10, and IL-17a levels, Mitogen, and Mitogen-Nil tube production levels were significantly different between the groups. Surprisingly, most of these measures were lowest in the severe COVID-19 patients' group. Using discriminant analysis effect size (LEfSe), Taxa of NM with significant abundance was determined. About 20 taxa with an LDA score > 4 were identified as candidate biomarkers. Some of these taxa showed a significant correlation with IL-1β and IL-10 Mitogen and Mitogen- Nil levels (R > 0.3 or < -0.3, p < 0.05). CONCLUSIONS The findings of this perticular study regarting the early stage of COVID-19 showed that in vitro cytokines production, studies might be more useful than the ordinary cytokines' blood level measurement. Besides, the study identified some NM species that could be candidate biomarkers in managing this infection. However, further detailed studies are needed in these fields.
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Affiliation(s)
- Mehmet Hursitoglu
- Internal Medicine Department, Basaksehir Cam & Sakura Sehir Hospital, University of Health Sciences, Istanbul, Turkey; Internal Medicine Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey.
| | - Nilgun Isıksacan
- Biochemistry Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Betul Erismis
- Internal Medicine Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Faruk Karandere
- Internal Medicine Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Alev Kural
- Biochemistry Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - A Baki Kumbasar
- Internal Medicine Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Kadriye Kart Yasar
- Clinical Microbiology and Infectious Diseases Department, Bakirkoy Dr. Sadi Konuk Training & Research Hospital, University of Health Sciences, Istanbul, Turkey
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Aganetti MA, Cruz CS, Galvão I, Engels DF, Ricci MF, Vieira AT. The Gut Microbiota and Immunopathophysiology. COMPREHENSIVE PHARMACOLOGY 2022:492-514. [DOI: 10.1016/b978-0-12-820472-6.00128-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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22
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Wang L, Wang Y, Zhang P, Song C, Pan F, Li G, Peng L, Yang Y, Wei Z, Huang F. Gut microbiota changes in patients with spondyloarthritis: A systematic review. Semin Arthritis Rheum 2021; 52:151925. [PMID: 34844732 DOI: 10.1016/j.semarthrit.2021.11.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 10/30/2021] [Accepted: 11/04/2021] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Gut microbiota has been proposed as a pivotal role in the progression of Spondyloarthritis (SpA), however diverse results remain to be synthesized. We performed a systematic review to collect evidence on the characteristic of the gut microbiota in patients with SpA, as compared to controls. METHODS We systematically searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through June 1, 2021 for studies that compared gut microbiota of cases with SpA versus healthy controls. RESULTS Of 3756 records identified, 28 studies from 23 articles were included in the analysis. Results of β-diversity showed SpA patients hold a significantly different microbial composition compared with controls. Several taxa-level differences of gut microbiota between SpA (and its subtypes) cases and controls were identified. Fourteen studies including only patients with ankylosing spondylitis (AS) reported increased amounts of Actinobacteria, Dialister, Streptococcus, and Clostridium bolteae, and decreased amounts of Bacteroidales and Parasutterella in AS cases versus controls in ≥ 3 studies. Dialister invisus was increased in axial-SpA cases versus controls in 3 studies. Bacteroides fragilis was increased in enthesitis-related arthritis (ERA) cases versus controls in 2 studies. For all SpA studies, Proteobacteria, Enterobacteriaceae, and Bacteroidaceae were increased, whereas Bacteroidetes, Bacteroidales, and Akkermansia were decreased in cases versus controls in ≥ 3 studies. Over 40% of the studies showed comparable data of both sex and age between cases and controls. CONCLUSION The microbial characteristics of SpA summarized in the systematic review laid the groundwork for evidence-based microbial treatment. The microbial variance among subtypes of SpA remains to be explored. Further studies are needed to elucidate how the altered microbiota participate in the pathogenesis of SpA.
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Affiliation(s)
- Lei Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Yiwen Wang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Pei Zhang
- School of Medicine, Nankai University, Tianjin, China
| | - Chuan Song
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China; Medical School of Chinese PLA, Beijing, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Gang Li
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China
| | - Lihua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhimin Wei
- Health Service Department of the Guard Bureau of the Joint Staff Department, Beijing, China.
| | - Feng Huang
- Department of Rheumatology and Immunology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
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Harjacek M. Immunopathophysiology of Juvenile Spondyloarthritis (jSpA): The "Out of the Box" View on Epigenetics, Neuroendocrine Pathways and Role of the Macrophage Migration Inhibitory Factor (MIF). Front Med (Lausanne) 2021; 8:700982. [PMID: 34692718 PMCID: PMC8526544 DOI: 10.3389/fmed.2021.700982] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 09/06/2021] [Indexed: 12/11/2022] Open
Abstract
Juvenile spondyloarthritis (jSpA) is a an umbrella term for heterogeneous group of related seronegative inflammatory disorders sharing common symptoms. Although it mainly affects children and adolescents, it often remains active during adulthood. Genetic and environmental factors are involved in its occurrence, although the exact underlying immunopathophysiology remains incompletely elucidated. Accumulated evidence suggests that, in affected patients, subclinical gut inflammation caused by intestinal dysbiosis, is pivotal to the future development of synovial-entheseal complex inflammation. While the predominant role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including jSpA, is firmly established, the role of the cytokine macrophage migration inhibitory factor (MIF) is generally overlooked. The purpose of this review is to discuss and emphasize the role of epigenetics, neuroendocrine pathways and the hypothalamic-pituitary (HPA) axis, and to propose a novel hypothesis of the role of decreased NLRP3 gene expression and possibly MIF in the early phases of jSpA development. The decreased NLRP3 gene expression in the latter, due to hypomethylation of promotor site, is (one of) the cause for inflammasome malfunction leading to gut dysbiosis observed in patients with early jSpA. In addition, we highlight the role of MIF in the complex innate, adaptive cellular and main effector cytokine network, Finally, since treatment of advanced bone pathology in SpA remains an unmet clinical need, I suggest possible new drug targets with the aim to ultimately improve treatment efficacy and long-term outcome of jSpA patients.
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Affiliation(s)
- Miroslav Harjacek
- Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
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Brim H, Taylor J, Abbas M, Vilmenay K, Daremipouran M, Varma S, Lee E, Pace B, Song-Naba WL, Gupta K, Nekhai S, O’Neil P, Ashktorab H. The gut microbiome in sickle cell disease: Characterization and potential implications. PLoS One 2021; 16:e0255956. [PMID: 34432825 PMCID: PMC8386827 DOI: 10.1371/journal.pone.0255956] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 07/27/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Sickle Cell Disease (SCD) is an inherited blood disorder that leads to hemolytic anemia, pain, organ damage and early mortality. It is characterized by polymerized deoxygenated hemoglobin, rigid sickle red blood cells and vaso-occlusive crises (VOC). Recurrent hypoxia-reperfusion injury in the gut of SCD patients could increase tissue injury, permeability, and bacterial translocation. In this context, the gut microbiome, a major player in health and disease, might have significant impact. This study sought to characterize the gut microbiome in SCD. METHODS Stool and saliva samples were collected from healthy controls (n = 14) and SCD subjects (n = 14). Stool samples were also collected from humanized SCD murine models including Berk, Townes and corresponding control mice. Amplified 16S rDNA was used for bacterial composition analysis using Next Generation Sequencing (NGS). Pairwise group analyses established differential bacterial groups at many taxonomy levels. Bacterial group abundance and differentials were established using DeSeq software. RESULTS A major dysbiosis was observed in SCD patients. The Firmicutes/Bacteroidetes ratio was lower in these patients. The following bacterial families were more abundant in SCD patients: Acetobacteraceae, Acidaminococcaceae, Candidatus Saccharibacteria, Peptostreptococcaceae, Bifidobacteriaceae, Veillonellaceae, Actinomycetaceae, Clostridiales, Bacteroidacbactereae and Fusobacteriaceae. This dysbiosis translated into 420 different operational taxonomic units (OTUs). Townes SCD mice also displayed gut microbiome dysbiosis as seen in human SCD. CONCLUSION A major dysbiosis was observed in SCD patients for bacteria that are known strong pro-inflammatory triggers. The Townes mouse showed dysbiosis as well and might serve as a good model to study gut microbiome modulation and its impact on SCD pathophysiology.
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Affiliation(s)
- Hassan Brim
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - James Taylor
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Muneer Abbas
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Kimberly Vilmenay
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Mohammad Daremipouran
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Sudhir Varma
- Hithru Analytics, Laurel, MD, United States of America
| | - Edward Lee
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Betty Pace
- University of Augusta, Augusta, GA, United States of America
| | - Waogwende L. Song-Naba
- Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America
| | - Kalpna Gupta
- Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America
- Hematology/Oncology, Department of Medicine, University of California Irvine, Irvine, CA, United States of America
- Southern California Institute for Research and Education, Long Beach VA Healthcare System, Long Beach, CA, United States of America
| | - Sergei Nekhai
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
| | - Patricia O’Neil
- Food and Drug Administration, Silver Spring, MD, United States of America
| | - Hassan Ashktorab
- Department of Pathology, Department of Medicine, Cancer Center, Microbiology and Center for Sickle Cell Disease, Howard University College of Medicine, Washington, DC, United States of America
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Berntson L. A pilot study of possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis. Pediatr Rheumatol Online J 2021; 19:88. [PMID: 34112181 PMCID: PMC8194161 DOI: 10.1186/s12969-021-00577-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/25/2021] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND To explore possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis. This diet has shown anti-inflammatory effect in children with inflammatory bowel disease. METHODS Twenty-two patients with juvenile idiopathic arthritis (age 6.3-17.3 years), with ≤2 inflamed joints and an erythrocyte sedimentation rate < 30 mm/h, were included in this explorative study. Fifteen children completing four weeks on the diet were evaluated. A dietician introduced parents and children to the diet, and two follow-ups were performed during the intervention. Conventional laboratory tests and multiplex analyses of 92 inflammatory proteins were used. Short-chain fatty acids in faecal samples were examined. RESULTS The diet significantly decreased morning stiffness (p = 0.003) and pain (p = 0.048). Physical function, assessed through the child health assessment questionnaire, improved (p = 0.022). Arthritis improved in five of the seven children with arthritis; in those seven, multiplex analyses showed a significant decrease in nine inflammatory proteins, including TNF-alpha (p = 0.028), after four weeks. Faecal butyrate, analysed in all 15 participants, increased significantly (p = 0.020). CONCLUSION The specific carbohydrate diet may have significant positive effects on arthritis in children with juvenile idiopathic arthritis, but further studies are needed. CLINICAL TRIALS IDENTIFIER NCT04205500 , 2019/12/17, retrospectively registered. URL: https://register.clinicaltrials.gov.
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Affiliation(s)
- Lillemor Berntson
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
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Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept. Pediatr Rheumatol Online J 2021; 19:55. [PMID: 33902613 PMCID: PMC8077782 DOI: 10.1186/s12969-021-00542-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 04/14/2021] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Alterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota. The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA. METHODS In this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons. RESULTS We did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept. Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes. There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept. CONCLUSIONS Treatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.
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Volkova A, Ruggles KV. Predictive Metagenomic Analysis of Autoimmune Disease Identifies Robust Autoimmunity and Disease Specific Microbial Signatures. Front Microbiol 2021; 12:621310. [PMID: 33746917 PMCID: PMC7969817 DOI: 10.3389/fmicb.2021.621310] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 02/11/2021] [Indexed: 12/12/2022] Open
Abstract
Within the last decade, numerous studies have demonstrated changes in the gut microbiome associated with specific autoimmune diseases. Due to differences in study design, data quality control, analysis and statistical methods, many results of these studies are inconsistent and incomparable. To better understand the relationship between the intestinal microbiome and autoimmunity, we have completed a comprehensive re-analysis of 42 studies focusing on the gut microbiome in 12 autoimmune diseases to identify a microbial signature predictive of multiple sclerosis (MS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and general autoimmune disease using both 16S rRNA sequencing data and shotgun metagenomics data. To do this, we used four machine learning algorithms, random forest, eXtreme Gradient Boosting (XGBoost), ridge regression, and support vector machine with radial kernel and recursive feature elimination to rank disease predictive taxa comparing disease vs. healthy participants and pairwise comparisons of each disease. Comparing the performance of these models, we found the two tree-based methods, XGBoost and random forest, most capable of handling sparse multidimensional data, to consistently produce the best results. Through this modeling, we identified a number of taxa consistently identified as dysregulated in a general autoimmune disease model including Odoribacter, Lachnospiraceae Clostridium, and Mogibacteriaceae implicating all as potential factors connecting the gut microbiome to autoimmune response. Further, we computed pairwise comparison models to identify disease specific taxa signatures highlighting a role for Peptostreptococcaceae and Ruminococcaceae Gemmiger in IBD and Akkermansia, Butyricicoccus, and Mogibacteriaceae in MS. We then connected a subset of these taxa with potential metabolic alterations based on metagenomic/metabolomic correlation analysis, identifying 215 metabolites associated with autoimmunity-predictive taxa.
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Affiliation(s)
- Angelina Volkova
- Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY, United States
| | - Kelly V. Ruggles
- Institute for Systems Genetics, New York University Grossman School of Medicine, New York, NY, United States
- Division of Translational Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, NY, United States
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Xin L, He F, Li S, Zhou ZX, Ma XL. Intestinal microbiota and juvenile idiopathic arthritis: current understanding and future prospective. World J Pediatr 2021; 17:40-51. [PMID: 32533534 DOI: 10.1007/s12519-020-00371-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 05/24/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Juvenile idiopathic arthritis (JIA) characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease, caused by both host genetic factors and environmental triggers. Recent evidence has mounted to focus on the intestinal microbiota, a potentially recognized set of environmental triggers affecting JIA development. Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA. DATA SOURCES We searched PubMed for animal and human studies publications with the search terms "intestinal microbiota or gut microbiota" and "juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis". RESULTS Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis. Alternatively, a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization, including cesarean section, formula feeding, and antibiotic exposure. Aberrant intestinal microbiota may influence the development of JIA by mediating host immune programming and by altering mucosal permeability. CONCLUSIONS Specific microbial factors may contribute to the pathogenesis of JIA. Intensive studies, however, are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships. Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.
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Affiliation(s)
- Le Xin
- Gynecological Minimal Invasive Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
| | - Feng He
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Yabao Road No. 2, Chaoyang District, Beijing, China
| | - Sen Li
- Department of Biochemistry and Immunology, Capital Institute of Pediatrics, Yabao Road No. 2, Chaoyang District, Beijing, China
| | - Zhi-Xuan Zhou
- Department of Rheumatology, Capital Institute of Pediatrics, Beijing, China
| | - Xiao-Lin Ma
- Department of Rheumatology, Capital Institute of Pediatrics, Beijing, China.
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Ling Z, Cheng Y, Yan X, Shao L, Liu X, Zhou D, Zhang L, Yu K, Zhao L. Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis. Front Immunol 2020; 11:590783. [PMID: 33391265 PMCID: PMC7772405 DOI: 10.3389/fimmu.2020.590783] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/16/2020] [Indexed: 12/14/2022] Open
Abstract
Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.
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Affiliation(s)
- Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yiwen Cheng
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiumei Yan
- Department of Laboratory Medicine, Lishui Second People’s Hospital, Lishui, China
| | - Li Shao
- Hangzhou Normal University, Hangzhou, China
- Institute of Translational Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
| | - Xia Liu
- Department of Intensive Care Unit, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Dajin Zhou
- Department of Laboratory Medicine, Lishui Second People’s Hospital, Lishui, China
| | - Lijuan Zhang
- Department of Laboratory Medicine, Lishui Second People’s Hospital, Lishui, China
| | - Kunqiang Yu
- Department of Laboratory Medicine, Lishui Second People’s Hospital, Lishui, China
| | - Longyou Zhao
- Department of Laboratory Medicine, Lishui Second People’s Hospital, Lishui, China
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Öman A, Dicksved J, Engstrand L, Berntson L. Fecal Microbiota in Untreated Children With Juvenile Idiopathic Arthritis: A Comparison With Healthy Children and Healthy Siblings. J Rheumatol 2020; 48:1589-1595. [PMID: 33262301 DOI: 10.3899/jrheum.200551] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2020] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Changes in the composition of gut microbiota have been suggested to be associated with juvenile idiopathic arthritis ( JIA). The objective in this study was to investigate if the diversity and composition of the fecal microbiota differed between children with JIA and healthy controls (HCs), and if the microbiota differed between children with JIA and their healthy siblings. METHODS In this multicenter, case-control study, fecal samples were collected from 75 children with JIA and 32 HCs. Eight of the HCs were siblings to 8 children with JIA, and they were compared only pairwise with their siblings. The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha diversity, community composition of microbiota, and relative abundances of taxa were compared between children with JIA and healthy unrelated controls as well as between children with JIA and healthy siblings. RESULTS Our data revealed no significant differences in α-diversity or community composition of microbiota between children with JIA, healthy unrelated controls, or healthy siblings. Analyses of relative abundances of phyla, families, and genera identified trends of differing abundances of some taxa in children with JIA, in comparison with both HCs and healthy siblings, but none of these findings were significant after adjustment for multiple comparisons. CONCLUSION There were no significant differences in the composition of fecal microbiota in children with JIA compared with HCs. The composition of microbiota in children with JIA did not differ significantly from that in their healthy siblings.
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Affiliation(s)
- Anders Öman
- The study was supported by grants from the Uppsala-Örebro Regional Research Council, the Gillbergska Foundation Uppsala, the Samariten Foundation for Paediatric Research, and the Swedish Rheumatism Association. 1A. Öman, MD, L. Berntson, MD, Associate Professor, Department of Women's and Children's Health, Uppsala University, Uppsala; 2J. Dicksved, PhD, Associate Professor, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala; 3L. Engstrand, MD, Professor, Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden. The authors have declared no conflicts of interest. Address correspondence to Dr. A. Öman, Unit for Pediatric Rheumatology, Department of Pediatrics, Uppsala University Hospital, S-75185 Uppsala, Sweden. . Accepted for publication November 11, 2020
| | - Johan Dicksved
- The study was supported by grants from the Uppsala-Örebro Regional Research Council, the Gillbergska Foundation Uppsala, the Samariten Foundation for Paediatric Research, and the Swedish Rheumatism Association. 1A. Öman, MD, L. Berntson, MD, Associate Professor, Department of Women's and Children's Health, Uppsala University, Uppsala; 2J. Dicksved, PhD, Associate Professor, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala; 3L. Engstrand, MD, Professor, Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden. The authors have declared no conflicts of interest. Address correspondence to Dr. A. Öman, Unit for Pediatric Rheumatology, Department of Pediatrics, Uppsala University Hospital, S-75185 Uppsala, Sweden. . Accepted for publication November 11, 2020
| | - Lars Engstrand
- The study was supported by grants from the Uppsala-Örebro Regional Research Council, the Gillbergska Foundation Uppsala, the Samariten Foundation for Paediatric Research, and the Swedish Rheumatism Association. 1A. Öman, MD, L. Berntson, MD, Associate Professor, Department of Women's and Children's Health, Uppsala University, Uppsala; 2J. Dicksved, PhD, Associate Professor, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala; 3L. Engstrand, MD, Professor, Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden. The authors have declared no conflicts of interest. Address correspondence to Dr. A. Öman, Unit for Pediatric Rheumatology, Department of Pediatrics, Uppsala University Hospital, S-75185 Uppsala, Sweden. . Accepted for publication November 11, 2020
| | - Lillemor Berntson
- The study was supported by grants from the Uppsala-Örebro Regional Research Council, the Gillbergska Foundation Uppsala, the Samariten Foundation for Paediatric Research, and the Swedish Rheumatism Association. 1A. Öman, MD, L. Berntson, MD, Associate Professor, Department of Women's and Children's Health, Uppsala University, Uppsala; 2J. Dicksved, PhD, Associate Professor, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala; 3L. Engstrand, MD, Professor, Center for Translational Microbiome Research, CTMR, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Science for Life Laboratory, Solna, Sweden. The authors have declared no conflicts of interest. Address correspondence to Dr. A. Öman, Unit for Pediatric Rheumatology, Department of Pediatrics, Uppsala University Hospital, S-75185 Uppsala, Sweden. . Accepted for publication November 11, 2020
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Frid P, Baraniya D, Halbig J, Rypdal V, Songstad NT, Rosèn A, Berstad JR, Flatø B, Alakwaa F, Gil EG, Cetrelli L, Chen T, Al-Hebshi NN, Nordal E, Al-Haroni M. Salivary Oral Microbiome of Children With Juvenile Idiopathic Arthritis: A Norwegian Cross-Sectional Study. Front Cell Infect Microbiol 2020; 10:602239. [PMID: 33251163 PMCID: PMC7672027 DOI: 10.3389/fcimb.2020.602239] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023] Open
Abstract
Background The oral microbiota has been connected to the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. The objective of this study was to characterize the salivary oral microbiome associated with juvenile idiopathic arthritis (JIA), and correlate it with the disease activity including gingival inflammation. Methods Fifty-nine patients with JIA (mean age, 12.6 ± 2.7 years) and 34 healthy controls (HC; mean age 12.3 ± 3.0 years) were consecutively recruited in this Norwegian cross-sectional study. Information about demographics, disease activity, medication history, frequency of tooth brushing and a modified version of the gingival bleeding index (GBI) and the simplified oral hygiene index (OHI-S) was obtained. Microbiome profiling of saliva samples was performed by sequencing of the V1-V3 region of the 16S rRNA gene, coupled with a species-level taxonomy assignment algorithm; QIIME, LEfSe and R-package for Spearman correlation matrix were used for downstream analysis. Results There were no significant differences between JIA and HC in alpha- and beta-diversity. However, differential abundance analysis revealed several taxa to be associated with JIA: TM7-G1, Solobacterium and Mogibacterium at the genus level; and Leptotrichia oral taxon 417, TM7-G1 oral taxon 352 and Capnocytophaga oral taxon 864 among others, at the species level. Haemophilus species, Leptotrichia oral taxon 223, and Bacillus subtilis, were associated with healthy controls. Gemella morbillorum, Leptotrichia sp. oral taxon 498 and Alloprevotella oral taxon 914 correlated positively with the composite juvenile arthritis 10-joint disease activity score (JADAS10), while Campylobacter oral taxon 44 among others, correlated with the number of active joints. Of all microbial markers identified, only Bacillus subtilis and Campylobacter oral taxon 44 maintained false discovery rate (FDR) < 0.1. Conclusions In this exploratory study of salivary oral microbiome we found similar alpha- and beta-diversity among children with JIA and healthy. Several taxa associated with chronic inflammation were found to be associated with JIA and disease activity, which warrants further investigation.
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Affiliation(s)
- Paula Frid
- Department of ENT, Division of Oral and Maxillofacial Surgery, University Hospital North Norway, Tromsø, Norway.,Public Dental Service Competence Centre of North Norway, Tromsø, Norway.,Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway
| | - Divyashri Baraniya
- Oral Microbiome Laboratory, Kornberg School of Dentistry, Temple University, Philadelphia, PA, United States
| | - Josefine Halbig
- Public Dental Service Competence Centre of North Norway, Tromsø, Norway.,Department of Clinical Dentistry, UiT the Arctic University of Norway, Tromsø, Norway
| | - Veronika Rypdal
- Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway.,Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Nils Thomas Songstad
- Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Annika Rosèn
- Department of Clinical Dentistry, University of Bergen, Bergen, Norway.,Department of Oral and Maxillofacial Surgery, Haukeland University Hospital, Bergen, Norway
| | - Johanna Rykke Berstad
- Department of ENT, Division of Oral and Maxillofacial Surgery, Oslo University Hospital, Oslo, Norway
| | - Berit Flatø
- Department of Rheumatology and Infectious Diseases, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Rheumatology, Oslo University Hospital, Oslo, Norway
| | - Fadhl Alakwaa
- Department of Computational Medicine and Bioinformatics, University Michigan, Ann Arbor, MI, United States
| | | | - Lena Cetrelli
- Center of Oral Health Services and Research (TkMidt), Trondheim, Norway
| | - Tsute Chen
- Department of Microbiology, Forsyth Institute, Cambridge, MA, United States
| | - Nezar Noor Al-Hebshi
- Oral Microbiome Laboratory, Kornberg School of Dentistry, Temple University, Philadelphia, PA, United States
| | - Ellen Nordal
- Department of Clinical Medicine, UiT the Arctic University of Norway, Tromsø, Norway.,Department of Pediatrics and Adolescence Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Mohammed Al-Haroni
- Department of Clinical Dentistry, UiT the Arctic University of Norway, Tromsø, Norway
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Iadanza E, Fabbri R, Bašić-ČiČak D, Amedei A, Telalovic JH. Gut microbiota and artificial intelligence approaches: A scoping review. HEALTH AND TECHNOLOGY 2020; 10:1343-1358. [DOI: 10.1007/s12553-020-00486-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 10/01/2020] [Indexed: 12/19/2022]
Abstract
AbstractThis article aims to provide a thorough overview of the use of Artificial Intelligence (AI) techniques in studying the gut microbiota and its role in the diagnosis and treatment of some important diseases. The association between microbiota and diseases, together with its clinical relevance, is still difficult to interpret. The advances in AI techniques, such as Machine Learning (ML) and Deep Learning (DL), can help clinicians in processing and interpreting these massive data sets. Two research groups have been involved in this Scoping Review, working in two different areas of Europe: Florence and Sarajevo. The papers included in the review describe the use of ML or DL methods applied to the study of human gut microbiota. In total, 1109 papers were considered in this study. After elimination, a final set of 16 articles was considered in the scoping review. Different AI techniques were applied in the reviewed papers. Some papers applied ML, while others applied DL techniques. 11 papers evaluated just different ML algorithms (ranging from one to eight algorithms applied to one dataset). The remaining five papers examined both ML and DL algorithms. The most applied ML algorithm was Random Forest and it also exhibited the best performances.
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DMARDs-Gut Microbiota Feedback: Implications in the Response to Therapy. Biomolecules 2020; 10:biom10111479. [PMID: 33114390 PMCID: PMC7692063 DOI: 10.3390/biom10111479] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/10/2020] [Accepted: 10/21/2020] [Indexed: 12/20/2022] Open
Abstract
Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.
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Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients. Microorganisms 2020; 8:microorganisms8101540. [PMID: 33036309 PMCID: PMC7650812 DOI: 10.3390/microorganisms8101540] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/01/2020] [Accepted: 10/02/2020] [Indexed: 01/15/2023] Open
Abstract
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.
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Pickert G, Wirtz S, Matzner J, Ashfaq-Khan M, Heck R, Rosigkeit S, Thies D, Surabattula R, Ehmann D, Wehkamp J, Aslam M, He G, Weigert A, Foerster F, Klotz L, Frick JS, Becker C, Bockamp E, Schuppan D. Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis. Gastroenterology 2020; 159:257-272.e17. [PMID: 32251667 DOI: 10.1053/j.gastro.2020.03.064] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 03/06/2020] [Accepted: 03/26/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice. METHODS C57BL/6 wild-type and Tlr4-/- mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10-/- mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative polymerase chain reaction and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry, and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays. RESULTS The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4-/- mice. CONCLUSIONS Consumption of wheat or wheat ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis.
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Affiliation(s)
- Geethanjali Pickert
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Stefan Wirtz
- Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany
| | - Johannes Matzner
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Muhammad Ashfaq-Khan
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Rosario Heck
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Sebastian Rosigkeit
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Dorothe Thies
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Rambabu Surabattula
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Dirk Ehmann
- Department of Internal Medicine 1, University Hospital Tübingen, Germany
| | - Jan Wehkamp
- Department of Internal Medicine 1, University Hospital Tübingen, Germany
| | - Misbah Aslam
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Guiwei He
- Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany
| | - Andreas Weigert
- Institute of Biochemistry I, Faculty of Medicine, Goethe University Frankfurt, Frankfurt, Germany
| | - Friedrich Foerster
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Department of Internal Medicine I, University Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Luisa Klotz
- Department of Neurology, University Hospital Muenster, Muenster, Germany
| | - Julia-Stefanie Frick
- Department for Medical Microbiology and Hygiene, Interfaculty Institute for Microbiology and Infection Medicine, University of Tübingen, Germany
| | - Christoph Becker
- Department of Medicine 1, Friedrich-Alexander-University, Erlangen, Germany
| | - Ernesto Bockamp
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany
| | - Detlef Schuppan
- Institute of Translational Immunology, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Research Center for Immunotherapy, Univ. Medical Center, Johannes Gutenberg University Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
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Ricciuto A, Sherman PM, Laxer RM. Gut microbiota in chronic inflammatory disorders: A focus on pediatric inflammatory bowel diseases and juvenile idiopathic arthritis. Clin Immunol 2020; 215:108415. [DOI: 10.1016/j.clim.2020.108415] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 04/06/2020] [Accepted: 04/06/2020] [Indexed: 12/16/2022]
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Wang X, Zhao Z, Tang N, Zhao Y, Xu J, Li L, Qian L, Zhang J, Fan Y. Microbial Community Analysis of Saliva and Biopsies in Patients With Oral Lichen Planus. Front Microbiol 2020; 11:629. [PMID: 32435231 PMCID: PMC7219021 DOI: 10.3389/fmicb.2020.00629] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 03/20/2020] [Indexed: 12/25/2022] Open
Abstract
The specific etiology and pathogenesis of oral lichen planus (OLP) remain elusive, and microbial dysbiosis may play an important role in OLP. We evaluated the saliva and tissue bacterial community of patients with OLP and identified the colonization of bacteria in OLP tissues. The saliva (n = 60) and tissue (n = 24) samples from OLP patients and the healthy controls were characterized by 16S rDNA gene sequencing and the bacterial signals in OLP tissues were detected by fluorescence in situ hybridization (FISH) targeting the bacterial 16S rDNA gene. Results indicate that the OLP tissue microbiome was different from the microbiota of OLP saliva. Compared with the healthy controls, Capnocytophaga and Gemella were higher in OLP saliva, while Escherichia–Shigella and Megasphaera were higher in OLP tissues, whereas seven taxa, including Carnobacteriaceae, Flavobacteriaceae, and Megasphaera, were enriched in both saliva and tissues of OLP patients. Furthermore, FISH found that the average optical density (AOD) of bacteria in the lamina propria of OLP tissues was higher than that of the healthy controls, and the AOD of bacteria in OLP epithelium and lamina propria was positively correlated. These data provide a different perspective for future investigation on the OLP microbiome.
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Affiliation(s)
- Xuewei Wang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Zhibai Zhao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Nan Tang
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Yuping Zhao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Juanyong Xu
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Liuyang Li
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Ling Qian
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
| | - Junfeng Zhang
- Medical School, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan Fan
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.,Department of Oral Medicine, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China
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Qian X, Liu YX, Ye X, Zheng W, Lv S, Mo M, Lin J, Wang W, Wang W, Zhang X, Lu M. Gut microbiota in children with juvenile idiopathic arthritis: characteristics, biomarker identification, and usefulness in clinical prediction. BMC Genomics 2020; 21:286. [PMID: 32264859 PMCID: PMC7137182 DOI: 10.1186/s12864-020-6703-0] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 03/25/2020] [Indexed: 12/19/2022] Open
Abstract
Background Recent studies have suggested that the gut microbiota is altered in children with juvenile idiopathic arthritis (JIA). However, age, sex, and body mass index (BMI) were not matched in the previous studies, and the results are inconsistent. We conducted an age-, sex-, and BMI-matched cross-sectional study to characterize the gut microbiota in children with JIA, and evaluate its potential in clinical prediction. Methods A total of 40 patients with JIA and 42 healthy controls, ranging from 1 to 16 years, were enrolled in this study. Fecal samples were collected for 16S rDNA sequencing. The data were analyzed using QIIME software and R packages. Specifically, the random forest model was used to identify biomarkers, and the receiver operating characteristic curve and the decision curve analysis were used to evaluate model performance. Results A total of 39 fecal samples from patients with JIA, and 42 fecal samples from healthy controls were sequenced successfully. The Chao 1 and Shannon–Wiener index in the JIA group were significantly lower than those in the control group, and the Bray-Curtis dissimilarity also differed significantly between the two groups. The relative abundance of 4 genera, Anaerostipes, Dialister, Lachnospira, and Roseburia, decreased significantly in the JIA group compared to those in the control group. The 4 genera included microbes that produce short-chain fatty acids (SCFAs) and were negatively correlated with some rheumatic indices. Moreover, 12 genera were identified as potential biomarkers by using the nested cross-validation function of the random forest. A random forest model constructed using these genera was able to differentiate the patients with JIA from the healthy controls, and the area under the receiver operating characteristic curve was 0.7975. The decision curve analysis indicated that the model had usefulness in clinical practice. Conclusions The gut microbiota in patients with JIA is altered and characterized by a decreased abundance of 4 SCFA-producing genera. The decreases in the 4 genera correlated with more serious clinical indices. Twelve genera could be used as biomarkers and predictors in clinical practice. Trial registration The study is registered online at the Chinese Clinical Trial Registry on 11 May 2018 (registration number: ChiCTR1800016110).
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Affiliation(s)
- Xubo Qian
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yong-Xin Liu
- State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | - Xiaohong Ye
- Department of Scientific Research Management and Medical Education, Jinhua Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang Province, China
| | - Wenjie Zheng
- Department of Paediatric Rheumatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
| | - Shaoxia Lv
- Nursing Department, Jiangnan Community Healthcare Center, Jinhua, Zhejiang Province, China
| | - Miaojun Mo
- Department of Pediatrics, Wenling Maternal and Child Healthcare Hospital, Wenling, Zhejiang Province, China
| | - Jinjing Lin
- Department of Pediatrics, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang Province, China
| | - Wenqin Wang
- Department of Rheumatology Immunology, Jinhua Municipal People's Hospital, Jinhua, Zhejiang Province, China
| | - Weihan Wang
- Department of Scientific Research Management and Medical Education, Jinhua Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang Province, China
| | - Xianning Zhang
- Department of Genetics, Institute of Genetics, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
| | - Meiping Lu
- Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
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Majumder S, Aggarwal A. Juvenile idiopathic arthritis and the gut microbiome: Where are we now? Best Pract Res Clin Rheumatol 2020; 33:101496. [PMID: 32171669 DOI: 10.1016/j.berh.2020.101496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies. Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success. The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.
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Affiliation(s)
- Sanjukta Majumder
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Amita Aggarwal
- Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
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40
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Lucafò M, Franzin M, Lagatolla C, Franca R, Bramuzzo M, Stocco G, Decorti G. Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients. Clin Transl Sci 2020; 13:238-259. [PMID: 31675176 PMCID: PMC7070880 DOI: 10.1111/cts.12722] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023] Open
Abstract
Diseases affecting the immune system, such as inflammatory bowel disease (IBD), juvenile idiopathic arthritis (JIA), and acute lymphoblastic leukemia (ALL), are pathological conditions affecting the pediatric population and are often associated with alterations in the intestinal microbiota, such as a decrease in bacterial diversity. Growing evidence suggests that gut microbiota can interfere with chemotherapeutic and immunosuppressant drugs, used in the treatment of these diseases, reducing or facilitating drug efficacy. In particular, the effect of intestinal microflora through translocation, immunomodulation, metabolism, enzymatic degradation, and reduction of bacterial diversity seems to be one of the reasons of interindividual variability in the therapeutic response. Although the extent of the role of intestinal microflora in chemotherapy and immunosuppression remains still unresolved, current evidence on bacterial compositional shifts will be taken in consideration together with clinical response to drugs for a better and personalized therapy. This review is focused on the effect of the intestinal microbiota on the efficacy of pharmacological therapy of agents used to treat IBD, JIA, and ALL.
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Affiliation(s)
- Marianna Lucafò
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”TriesteItaly
| | - Martina Franzin
- PhD Course in Reproductive and Developmental SciencesUniversity of TriesteTriesteItaly
| | | | - Raffaella Franca
- Department of Medical, Surgical and Health SciencesUniversity of TriesteTriesteItaly
| | - Matteo Bramuzzo
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”TriesteItaly
| | - Gabriele Stocco
- Department of Life SciencesUniversity of TriesteTriesteItaly
| | - Giuliana Decorti
- Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”TriesteItaly
- Department of Medical, Surgical and Health SciencesUniversity of TriesteTriesteItaly
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Arvonen M, Vänni P, Sarangi AN, V Tejesvi M, Vähäsalo P, Aggarwal A, Stoll ML. Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray? Immunol Rev 2019; 294:9-26. [DOI: 10.1111/imr.12826] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 11/07/2019] [Indexed: 12/16/2022]
Affiliation(s)
- Miika Arvonen
- Department of Pediatrics Kuopio University HospitalUniversity of Eastern Finland Kuopio Finland
- PEDEGO Research Unit Faculty of Medicine University of Oulu Oulu Finland
| | - Petri Vänni
- PEDEGO Research Unit Faculty of Medicine University of Oulu Oulu Finland
- Genobiomics LLC Oulu Finland
| | - Aditya Narayan Sarangi
- Biomedical Informatics Center Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow India
| | - Mysore V Tejesvi
- Genobiomics LLC Oulu Finland
- Department of Ecology and Genetics University of Oulu Oulu Finland
| | - Paula Vähäsalo
- PEDEGO Research Unit Faculty of Medicine University of Oulu Oulu Finland
- Department of Children and Adolescents Oulu University Hospital Oulu Finland
- Medical Research Center Oulu Oulu Finland
| | - Amita Aggarwal
- Department of Clinical Immunology & Rheumatology Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow India
| | - Matthew L Stoll
- Department of Pediatrics University of Alabama at Birmingham Birmingham AL USA
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42
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Dong YQ, Wang W, Li J, Ma MS, Zhong LQ, Wei QJ, Song HM. Characterization of microbiota in systemic-onset juvenile idiopathic arthritis with different disease severities. World J Clin Cases 2019; 7:2734-2745. [PMID: 31616689 PMCID: PMC6789395 DOI: 10.12998/wjcc.v7.i18.2734] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 07/17/2019] [Accepted: 07/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of most serious subtypes of juvenile idiopathic arthritis. Although the pathogenesis of SoJIA remains unclear, several studies have suggested a correlation between gut dysbiosis and JIA. Further understanding of the intestinal microbiome may help to establish alternative ways to treat, or even prevent, the disease.
AIM To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters.
METHODS We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital. Children who were diagnosed with SoJIA at our institution and followed for a minimum period of six months after diagnosis were recruited for the study. Healthy children were recruited as a control group (HS group) during the same period. Clinical data and stool samples were collected from SoJIA patients when they visited the hospital.
RESULTS The SoJIA group included 17 active and 15 inactive consecutively recruited children; the control group consisted of 32 children. Firmicutes and Bacteroidetes were the two most abundant phyla among the total sample of SoJIA children and controls. There was a significant difference among the three groups in observed species, which was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA group and then HS group (Active-SoJIA vs HS: P = 0.000; and Inactive-SoJIA vs HS: P = 0.005). We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients (3.28 ± 4.47 in Active-SoJIA, 5.36 ± 8.39 in Inactive-SoJIA, and 5.67 ± 3.92 in HS). We also observed decreased abundances of Ruminococcaceae (14.9% in Active-SoJIA, 17.3% in Inactive-SoJIA, and 22.8% in HS; Active-SoJIA vs HS: P = 0.005) and Faecalibacterium (5.1% in Active-SoJIA, 9.9% in Inactive-SoJIA, and 13.0% in HS; Active-SoJIA vs HS: P = 0.000) in SoJIA compared with HS. By contrast, the abundance of Bacteroidaceae was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA and HS groups (16.5% in Active-SoJIA, 12.8% in Inactive-SoJIA, and 9.7% in HS; Active-SoJIA vs HS: P = 0.03). The Spearman correlation analysis revealed a negative correlation between Proteobacteria or Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints (JADAS-27).
CONCLUSION The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.
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Affiliation(s)
- Yan-Qing Dong
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei Wang
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ji Li
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ming-Sheng Ma
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lin-Qing Zhong
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Qi-Jiao Wei
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hong-Mei Song
- Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Sun L, Jia H, Li J, Yu M, Yang Y, Tian D, Zhang H, Zou Z. Cecal Gut Microbiota and Metabolites Might Contribute to the Severity of Acute Myocardial Ischemia by Impacting the Intestinal Permeability, Oxidative Stress, and Energy Metabolism. Front Microbiol 2019; 10:1745. [PMID: 31428065 PMCID: PMC6687875 DOI: 10.3389/fmicb.2019.01745] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 07/15/2019] [Indexed: 12/13/2022] Open
Abstract
Emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease. Here, we performed 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabolomics to investigate the gut microbiome and metabolomes of cecal contents in the isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rats. As expected, considerable gut microbiota alterations were observed in the AMI rats compared with the control rats, paralleling with intestinal inflammation and apoptosis. At phylum level, the abundance of Firmicutes was significantly decreased, whereas the abundance of Bacteroidetes and Spirochaetae was strikingly enriched in the AMI group. At genus level, the significant alteration of genera Treponema 2, Rikenellaceae RC9 gut group, Prevotellaceae UCG-003, and Bacteroides may contribute to the pathogenesis of AMI. These altered microbiota might influence the intestinal permeability and subsequently impair intestinal barrier and stimulate gut inflammation. Consistently, significantly metabolic differences of cecal contents between the AMI and control groups were revealed, and threonic acid, L-urobilin and L-urobilinogen were considered the most associated cecal metabolites with AMI. These strikingly altered metabolites were mainly related to energy metabolism and oxidative stress which could lead to apoptosis and further affect gut barrier. Ultimately, we revealed the potential link of these altered gut microbiota/metabolomes and intestinal inflammatory factors and apoptotic proteins and further confirmed their intimate connections with intestinal inflammation and gut barrier. Our findings depict uncovered potential relationship among the gut microbiome, cecal metabolomes and AMI.
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Affiliation(s)
- Lili Sun
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hongmei Jia
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jiaojiao Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Meng Yu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yong Yang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Dong Tian
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hongwu Zhang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Zhongmei Zou
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Bang S, Yoo D, Kim SJ, Jhang S, Cho S, Kim H. Establishment and evaluation of prediction model for multiple disease classification based on gut microbial data. Sci Rep 2019; 9:10189. [PMID: 31308384 PMCID: PMC6629854 DOI: 10.1038/s41598-019-46249-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 04/12/2019] [Indexed: 12/17/2022] Open
Abstract
Diseases prediction has been performed by machine learning approaches with various biological data. One of the representative data is the gut microbial community, which interacts with the host's immune system. The abundance of a few microorganisms has been used as markers to predict diverse diseases. In this study, we hypothesized that multi-classification using machine learning approach could distinguish the gut microbiome from following six diseases: multiple sclerosis, juvenile idiopathic arthritis, myalgic encephalomyelitis/chronic fatigue syndrome, acquired immune deficiency syndrome, stroke and colorectal cancer. We used the abundance of microorganisms at five taxonomy levels as features in 696 samples collected from different studies to establish the best prediction model. We built classification models based on four multi-class classifiers and two feature selection methods including a forward selection and a backward elimination. As a result, we found that the performance of classification is improved as we use the lower taxonomy levels of features; the highest performance was observed at the genus level. Among four classifiers, LogitBoost-based prediction model outperformed other classifiers. Also, we suggested the optimal feature subsets at the genus-level obtained by backward elimination. We believe the selected feature subsets could be used as markers to distinguish various diseases simultaneously. The finding in this study suggests the potential use of selected features for the diagnosis of several diseases.
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Affiliation(s)
- Sohyun Bang
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742, Republic of Korea
- C&K genomics, Seoul National University Research Park, Seoul, 151-919, Republic of Korea
| | - DongAhn Yoo
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742, Republic of Korea
| | - Soo-Jin Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea
| | - Soyun Jhang
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742, Republic of Korea
- C&K genomics, Seoul National University Research Park, Seoul, 151-919, Republic of Korea
| | - Seoae Cho
- C&K genomics, Seoul National University Research Park, Seoul, 151-919, Republic of Korea
| | - Heebal Kim
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, 151-742, Republic of Korea.
- C&K genomics, Seoul National University Research Park, Seoul, 151-919, Republic of Korea.
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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Horton DB. Juvenile Idiopathic Arthritis and the Gut Microbiome: More Clues, More Questions. Arthritis Rheumatol 2019; 71:842-845. [PMID: 30667170 PMCID: PMC6536314 DOI: 10.1002/art.40842] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 01/17/2019] [Indexed: 12/22/2022]
Affiliation(s)
- Daniel B Horton
- Rutgers Robert Wood Johnson Medical School, Rutgers Center for Pharmacoepidemiology and Treatment Science, Rutgers School of Public Health, New Brunswick, New Jersey
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46
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van Dijkhuizen EHP, Del Chierico F, Malattia C, Russo A, Pires Marafon D, Ter Haar NM, Magni-Manzoni S, Vastert SJ, Dallapiccola B, Prakken B, Martini A, De Benedetti F, Putignani L. Microbiome Analytics of the Gut Microbiota in Patients With Juvenile Idiopathic Arthritis: A Longitudinal Observational Cohort Study. Arthritis Rheumatol 2019; 71:1000-1010. [PMID: 30592383 PMCID: PMC6593809 DOI: 10.1002/art.40827] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 12/20/2018] [Indexed: 12/14/2022]
Abstract
Objective To assess the composition of gut microbiota in Italian and Dutch patients with juvenile idiopathic arthritis (JIA) at baseline, with inactive disease, and with persistent activity compared to healthy controls. Methods In a multicenter, prospective, observational cohort study, fecal samples were collected at baseline from 78 Italian and 21 Dutch treatment‐naive JIA patients with <6 months of disease duration and compared to 107 geographically matched samples from healthy children. Forty‐four follow‐up samples from patients with inactive disease and 25 follow‐up samples from patients with persistent activity were analyzed. Gut microbiota composition was determined by 16S ribosomal RNA–based metagenomics. Alpha‐ and β‐diversity were computed, and log ratios of relative abundance were compared between patients and healthy controls using random forest models and logistic regression. Results Baseline samples from Italian patients showed reduced richness compared to healthy controls (P < 0.001). Random forest models distinguished between Italian patient baseline samples and healthy controls and suggested differences between Dutch patient samples and healthy controls (areas under the curve >0.99 and 0.71, respectively). The operational taxonomic units (OTUs) of Erysipelotrichaceae (increased in patients), Allobaculum (decreased in patients), and Faecalibacterium prausnitzii (increased in patients) showed different relative abundance in Italian patient baseline samples compared to controls after controlling for multiple comparisons. Some OTUs differed between Dutch patient samples and healthy controls, but no evidence remained after controlling for multiple comparisons. No differences were found in paired analysis between Italian patient baseline and inactive disease samples. Conclusion Our findings show evidence for dysbiosis in JIA patients. Only patient/control status, age, and geographic origin appear to be drivers of the microbiota profiles, regardless of disease activity stage, inflammation, and markers of autoimmunity.
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Affiliation(s)
- E H Pieter van Dijkhuizen
- Istituto Giannina Gaslini, Genoa, Italy, and University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
| | | | - Clara Malattia
- Istituto Giannina Gaslini and Università degli Studi di Genoa, Genoa, Italy
| | | | | | - Nienke M Ter Haar
- University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
| | | | - Sebastiaan J Vastert
- University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
| | | | - Berent Prakken
- University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
| | - Alberto Martini
- Istituto Giannina Gaslini and Università degli Studi di Genoa, Genoa, Italy
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De Filippo C, Di Paola M, Giani T, Tirelli F, Cimaz R. Gut microbiota in children and altered profiles in juvenile idiopathic arthritis. J Autoimmun 2019; 98:1-12. [PMID: 30638708 DOI: 10.1016/j.jaut.2019.01.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 12/19/2018] [Accepted: 01/02/2019] [Indexed: 12/18/2022]
Abstract
Microbial diversity plays a key role in the maintenance of intestinal homeostasis and in the development of the immune system in the gut mucosa. Maybe one of the most important function of our gut microbiota is the immune system education, in particular the discrimination of friends from foes that occurs during childhood. In addition to bacterial antigens, several metabolites of microbial origin have a crucial role in training of the immune system, such as Short Chain Fatty Acids (SCFAs). There are many evidences on the role of the gut microbiota in rheumatic diseases, in particular modifications of microbiota composition causing dysbiosis that, in turn, can induce gut permeability, and thus immunological imbalance and trigger inflammation. In particular, immune cells can reach extra-intestinal sites, such as joints and trigger local inflammation. Childhood is a crucial period of life for development and evolution of the gut microbiota, especially for the acquisition of fundamental functions such as immunotolerance of commensal microorganisms. For this reason, gut dysbiosis is gaining interest as a potential pathogenetic factor for Juvenile Idiopathic Arthritis (JIA). Here we summarized the studies conducted on JIA patients in which a pro-arthritogenic microbial profiles has been observed; this, together with a depletion of microbial biodiversity, clearly distinguish patients' from healthy subjects' microbiota. Further studies are however needed to better clarify the role of microbiota in JIA pathogenesis.
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Affiliation(s)
- Carlotta De Filippo
- Institute of Biology and Agrarian Biotechnology (IBBA), National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, Italy
| | - Monica Di Paola
- Department of Biology, University of Florence, Via Madonna del Piano 6, 50019 Sesto Fiorentino, Florence, Italy
| | - Teresa Giani
- Rheumatology Unit, Anna Meyer Children's Hospital, University of Florence, Viale G. Pieraccini 24, 50139, Florence, Italy; Department of Medica Biotechnologies, University of Siena, Viale Mario Bracci, 16 53100, Siena, Italy
| | - Francesca Tirelli
- Rheumatology Unit, Anna Meyer Children's Hospital, University of Florence, Viale G. Pieraccini 24, 50139, Florence, Italy
| | - Rolando Cimaz
- Rheumatology Unit, Anna Meyer Children's Hospital, University of Florence, Viale G. Pieraccini 24, 50139, Florence, Italy; Department of Neuroscience, Psychology, Drug Research and Child Health, Meyer Children's Hospital, University of Florence, Viale G. Pieraccini 6, 50139, Florence, Italy.
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48
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Abstract
Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU. Finally, potential therapeutic avenues to target the microbiota for the clinical management of AAU and SpA are outlined.
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Affiliation(s)
- James T Rosenbaum
- Departments of Ophthalmology, Medicine and Cell Biology, Oregon Health and Science University, Portland, OR, USA
- Legacy Devers Eye Institute, Portland, OR, USA
| | - Mark Asquith
- Department of Medicine, Oregon Health and Science University, Portland, OR, USA.
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49
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Stefanov S, Ganeva M, Stoilov N, Boyadzhieva V, Telcharova-Mihaylovska A. The role of gut microbiota in juvenile idiopathic arthritis. BIOTECHNOL BIOTEC EQ 2018. [DOI: 10.1080/13102818.2018.1512376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Affiliation(s)
- Stefan Stefanov
- Department of Pediatric Rheumatology, University Children’s Hospital, Medical University of Sofia, Sofia, Bulgaria
| | - Margarita Ganeva
- Department of Pediatric Rheumatology, University Children’s Hospital, Medical University of Sofia, Sofia, Bulgaria
| | - Nikolay Stoilov
- Clinic of Rheumatology, University Hospital ‘St. I. Rilski’, Medical University of Sofia, Sofia, Bulgaria
| | - Vladimira Boyadzhieva
- Clinic of Rheumatology, University Hospital ‘St. I. Rilski’, Medical University of Sofia, Sofia, Bulgaria
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50
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Yacoub R, Jacob A, Wlaschin J, McGregor M, Quigg RJ, Alexander JJ. Lupus: The microbiome angle. Immunobiology 2018; 223:460-465. [DOI: 10.1016/j.imbio.2017.11.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 11/15/2017] [Accepted: 11/15/2017] [Indexed: 02/08/2023]
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