Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease

Prabha Chandrasekaran, Yu Han, Christa S. Zerbe, Theo Heller, Suk See DeRavin, Samantha A. Kreuzberg, Beatriz E. Marciano, Yik Siu, Drew R. Jones, Roshini S. Abraham, Michael C. Stephens, Amy M. Tsou, Scott Snapper, Sean Conlan, Poorani Subramanian, Mariam Quinones, Caroline Grou, Virginie Calderon, Clayton Deming, Jennifer W. LeidingDanielle E. Arnold, Brent R. Logan, Linda M. Griffith, Aleksandra Petrovic, Talal I. Mousallem, Neena Kapoor, Jennifer R. Heimall, Jessie L. Barnum, Malika Kapadia, Nicola Wright, Ahmad Rayes, Sharat Chandra, Larisa A. Broglie, Deepak Chellapandian, Christin L. Deal, Eyal Grunebaum, Stephanie Si Lim, Kanwaldeep Mallhi, Rebecca A. Marsh, Luis Murguia-Favela, Suhag Parikh, Fabien Touzot, Morton J. Cowan, Christopher C. Dvorak, Elie Haddad, Donald B. Kohn, Luigi D. Notarangelo, Sung Yun Pai, Jennifer M. Puck, Michael A. Pulsipher, Troy R. Torgerson, Elizabeth M. Kang, Harry L. Malech, Julia A. Segre, Clare E. Bryant, Steven M. Holland, Emilia Liana Falcone

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1619-1633.e11
JournalJournal of Allergy and Clinical Immunology
Volume152
Issue number6
DOIs
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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