دورية أكاديمية
Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.
العنوان: | Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease. |
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المؤلفون: | Chandrasekaran P; Laboratory of Clinical Investigations, National Institutes of Aging, Baltimore, Md., Han Y; Division of Molecular Genetics and Pathology, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Zerbe CS; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Heller T; Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Md., DeRavin SS; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Kreuzberg SA; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Marciano BE; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Siu Y; Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY., Jones DR; Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY., Abraham RS; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio., Stephens MC; Department of Pediatric Gastroenterology, Mayo Clinic, Rochester, Minn., Tsou AM; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Mass; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, NY., Snapper S; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Mass., Conlan S; National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md., Subramanian P; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md., Quinones M; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md., Grou C; Bioinformatics Core, Montreal Clinical Research Institute (IRCM), Montreal, Quebec, Canada., Calderon V; Bioinformatics Core, Montreal Clinical Research Institute (IRCM), Montreal, Quebec, Canada., Deming C; National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md., Leiding JW; Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, Md., Arnold DE; Immune Deficiency-Cellular Therapy Program, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Md., Logan BR; Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wis., Griffith LM; Division of Allergy, Immunology, and Transplantation, NIAID, NIH, Bethesda, Md., Petrovic A; Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital and Research Center, Seattle, Wash., Mousallem TI; Department of Pediatrics, Duke University Medical Center, Durham, NC., Kapoor N; Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, Calif., Heimall JR; Division of Allergy and Immunology, Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa., Barnum JL; Division of Blood and Marrow Transplantation and Cellular Therapies, University of Pittsburgh Medical Center (UPMC) and Children's Hospital of Pittsburgh, Pittsburgh, Pa., Kapadia M; Department of Pediatrics, Harvard University Medical School, Boston, Mass., Wright N; Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada., Rayes A; Intermountain Primary Children's Hospital, University of Utah, Salt Lake City, Utah., Chandra S; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio., Broglie LA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis., Chellapandian D; Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, Fla., Deal CL; Division of Allergy and Immunology, UPMC, Children's Hospital of Pittsburgh, Pittsburgh, Pa., Grunebaum E; Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Lim SS; Department of Pediatrics, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, Hawaii; University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawaii., Mallhi K; Fred Hutchinson Cancer Research Center, Seattle, Wash., Marsh RA; Cincinnati Children's Hospital Medical Center, and University of Cincinnati, Cincinnati, Ohio., Murguia-Favela L; Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada., Parikh S; Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga., Touzot F; Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada., Cowan MJ; University of California San Francisco Benioff Children's Hospital, San Francisco, Calif., Dvorak CC; University of California San Francisco Benioff Children's Hospital, San Francisco, Calif., Haddad E; Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada., Kohn DB; Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Calif., Notarangelo LD; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Pai SY; Immune Deficiency-Cellular Therapy Program, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Md., Puck JM; University of California San Francisco Benioff Children's Hospital, San Francisco, Calif., Pulsipher MA; Division of Pediatric Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, Utah., Torgerson TR; Allen Institute for Immunology, Seattle, Wash., Kang EM; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Malech HL; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Segre JA; National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md., Bryant CE; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Holland SM; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md., Falcone EL; Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md; Department of Microbiology, Infectious Diseases, and Immunology, Université de Montréal, Montreal, Quebec, Canada; Center for Immunity, Inflammation and Infectious Diseases, IRCM, Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. Electronic address: emilia.falcone@ircm.qc.ca. |
المصدر: | The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Dec; Vol. 152 (6), pp. 1619-1633.e11. Date of Electronic Publication: 2023 Sep 01. |
نوع المنشور: | Observational Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Intramural |
اللغة: | English |
بيانات الدورية: | Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: St Louis, Mosby. |
مواضيع طبية MeSH: | Granulomatous Disease, Chronic*/genetics , Gastrointestinal Microbiome* , Inflammatory Bowel Diseases*, Humans ; NADPH Oxidases ; Cross-Sectional Studies |
مستخلص: | Background: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. Objective: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. Methods: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. Results: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. Conclusion: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | U01 TR001263 United States TR NCATS NIH HHS; U54 AI082973 United States AI NIAID NIH HHS; P30 CA042014 United States CA NCI NIH HHS; ZIA AI001222 United States ImNIH Intramural NIH HHS; U54 NS064808 United States NS NINDS NIH HHS; ZIA AI001216 United States ImNIH Intramural NIH HHS; UG1 HL069254 United States HL NHLBI NIH HHS; U10 HL069254 United States HL NHLBI NIH HHS; U01 AI126612 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: CGD; Chronic granulomatous disease; IBD; NADPH oxidase; dysbiosis; inborn errors of immunity; inflammatory bowel disease; intestinal inflammation; metabolome; microbiome; primary immune deficiency |
سلسلة جزيئية: | ClinicalTrials.gov NCT02082353 |
المشرفين على المادة: | EC 1.6.3.- (NADPH Oxidases) |
تواريخ الأحداث: | Date Created: 20230902 Date Completed: 20231216 Latest Revision: 20240728 |
رمز التحديث: | 20240728 |
مُعرف محوري في PubMed: | PMC11279821 |
DOI: | 10.1016/j.jaci.2023.07.022 |
PMID: | 37659505 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1097-6825 |
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DOI: | 10.1016/j.jaci.2023.07.022 |