RT Journal
A1 Oh, Julia
A1 Freeman, Alexandra F.
A1 NISC Comparative Sequencing Program
A1 Park, Morgan
A1 Sokolic, Robert
A1 Candotti, Fabio
A1 Holland, Steven M.
A1 Segre, Julia A.
A1 Kong, Heidi H.
T1 The altered landscape of the human skin microbiome in patients with primary immunodeficiencies
JF Genome Research 
JO Genome Research 
YR 2013 
FD December 01 
VO 23 
IS 12 
SP 2103 
OP 2114 
DO 10.1101/gr.159467.113 
UL http://genome.cshlp.org/content/23/12/2103.abstract 
AB While landmark studies have shown that microbiota activate and educate host immunity, how immune systems shape microbiomes and contribute to disease is incompletely characterized. Primary immunodeficiency (PID) patients suffer recurrent microbial infections, providing a unique opportunity to address this issue. To investigate the potential influence of host immunity on the skin microbiome, we examined skin microbiomes in patients with rare monogenic PIDs: hyper-IgE (STAT3-deficient), Wiskott-Aldrich, and dedicator of cytokinesis 8 syndromes. While specific immunologic defects differ, a shared hallmark is atopic dermatitis (AD)–like eczema. We compared bacterial and fungal skin microbiomes (41 PID, 13 AD, 49 healthy controls) at four clinically relevant sites representing the major skin microenvironments. PID skin displayed increased ecological permissiveness with altered population structures, decreased site specificity and temporal stability, and colonization with microbial species not observed in controls, including Clostridium species and Serratia marcescens. Elevated fungal diversity and increased representation of opportunistic fungi (Candida, Aspergillus) supported increased PID skin permissiveness, suggesting that skin may serve as a reservoir for the recurrent fungal infections observed in these patients. The overarching theme of increased ecological permissiveness in PID skin was counterbalanced by the maintenance of a phylum barrier in which colonization remained restricted to typical human-associated phyla. Clinical parameters, including markers of disease severity, were positively correlated with prevalence of Staphylococcus, Corynebacterium, and other less abundant taxa. This study examines differences in microbial colonization and community stability in PID skin and informs our understanding of host–microbiome interactions, suggesting a bidirectional dialogue between skin commensals and the host organism.