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