Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.

CGD Chronic granulomatous disease IBD NADPH oxidase dysbiosis inborn errors of immunity inflammatory bowel disease intestinal inflammation metabolome microbiome primary immune deficiency

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 04 03 2023
revised: 18 07 2023
accepted: 27 07 2023
pubmed: 3 9 2023
medline: 3 9 2023
entrez: 2 9 2023
Statut: ppublish

Résumé

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. We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. 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. 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. Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

Sections du résumé

BACKGROUND 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 OBJECTIVE
We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD.
METHODS 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 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 CONCLUSIONS
Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

Identifiants

DOI: 10.1016/j.jaci.2023.07.022 PMID: 37659505
pubmed: 37659505
pii: S0091-6749(23)01101-6
doi: 10.1016/j.jaci.2023.07.022
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1619-1633.e11

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Prabha Chandrasekaran (P)

Laboratory of Clinical Investigations, National Institutes of Aging, Baltimore, Md.

Yu 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.

Christa S Zerbe (CS)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Theo Heller (T)

Translational Hepatology Section, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, Md.

Suk See DeRavin (SS)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Samantha A Kreuzberg (SA)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Beatriz E Marciano (BE)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Yik Siu (Y)

Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY.

Drew R Jones (DR)

Department of Biochemistry and Molecular Pharmacology, New York University Langone Health, New York, NY.

Roshini S Abraham (RS)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio.

Michael C Stephens (MC)

Department of Pediatric Gastroenterology, Mayo Clinic, Rochester, Minn.

Amy M 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.

Scott Snapper (S)

Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Mass.

Sean Conlan (S)

National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md.

Poorani Subramanian (P)

Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md.

Mariam Quinones (M)

Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, Md.

Caroline Grou (C)

Bioinformatics Core, Montreal Clinical Research Institute (IRCM), Montreal, Quebec, Canada.

Virginie Calderon (V)

Bioinformatics Core, Montreal Clinical Research Institute (IRCM), Montreal, Quebec, Canada.

Clayton Deming (C)

National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md.

Jennifer W Leiding (JW)

Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, Md.

Danielle E Arnold (DE)

Immune Deficiency-Cellular Therapy Program, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Md.

Brent R Logan (BR)

Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, Wis.

Linda M Griffith (LM)

Division of Allergy, Immunology, and Transplantation, NIAID, NIH, Bethesda, Md.

Aleksandra Petrovic (A)

Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital and Research Center, Seattle, Wash.

Talal I Mousallem (TI)

Department of Pediatrics, Duke University Medical Center, Durham, NC.

Neena Kapoor (N)

Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, Calif.

Jennifer R 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.

Jessie L 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.

Malika Kapadia (M)

Department of Pediatrics, Harvard University Medical School, Boston, Mass.

Nicola Wright (N)

Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.

Ahmad Rayes (A)

Intermountain Primary Children's Hospital, University of Utah, Salt Lake City, Utah.

Sharat 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.

Larisa A Broglie (LA)

Division of Pediatric Hematology-Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wis.

Deepak Chellapandian (D)

Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, Fla.

Christin L Deal (CL)

Division of Allergy and Immunology, UPMC, Children's Hospital of Pittsburgh, Pittsburgh, Pa.

Eyal 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.

Stephanie Si 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.

Kanwaldeep Mallhi (K)

Fred Hutchinson Cancer Research Center, Seattle, Wash.

Rebecca A Marsh (RA)

Cincinnati Children's Hospital Medical Center, and University of Cincinnati, Cincinnati, Ohio.

Luis Murguia-Favela (L)

Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.

Suhag Parikh (S)

Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.

Fabien 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.

Morton J Cowan (MJ)

University of California San Francisco Benioff Children's Hospital, San Francisco, Calif.

Christopher C Dvorak (CC)

University of California San Francisco Benioff Children's Hospital, San Francisco, Calif.

Elie 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.

Donald B Kohn (DB)

Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Calif.

Luigi D Notarangelo (LD)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Sung-Yun Pai (SY)

Immune Deficiency-Cellular Therapy Program, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Md.

Jennifer M Puck (JM)

University of California San Francisco Benioff Children's Hospital, San Francisco, Calif.

Michael A 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.

Troy R Torgerson (TR)

Allen Institute for Immunology, Seattle, Wash.

Elizabeth M Kang (EM)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Harry L Malech (HL)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Julia A Segre (JA)

National Human Genome Research Institute (NHGRI), NIH, Bethesda, Md.

Clare E Bryant (CE)

Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Steven M Holland (SM)

Laboratory of Clinical Immunology and Microbiology (LCIM), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Md.

Emilia Liana 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.

Classifications MeSH