Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis
Loreto Abusleme, … , Heidi H. Kong, Niki M. Moutsopoulos
Loreto Abusleme, … , Heidi H. Kong, Niki M. Moutsopoulos
Published September 6, 2018
Citation Information: JCI Insight. 2018;3(17):e122061. https://doi.org/10.1172/jci.insight.122061.
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Research Article Infectious disease Microbiology

Human defects in STAT3 promote oral mucosal fungal and bacterial dysbiosis

Abstract

Studies in patients with genetic defects can provide unique insights regarding the role of specific genes and pathways in humans. Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections. Our studies aimed to comprehensively evaluate consequences of STAT3 deficiency on the oral commensal microbiome. We characterized fungal and bacterial communities in AD-HIES in the presence and absence of oral fungal infection compared with healthy volunteers. Analyses of oral mucosal fungal communities in AD-HIES revealed severe dysbiosis with dominance of Candida albicans (C. albicans) in actively infected patients and minimal representation of health-associated fungi and/or opportunists. Bacterial communities also displayed dysbiosis in AD-HIES, particularly in the setting of active Candida infection. Active candidiasis was associated with decreased microbial diversity and enrichment of the streptococci Streptococcus oralis (S. oralis) and S. mutans, suggesting an interkingdom interaction of C. albicans with oral streptococci. Increased abundance of S. mutans was consistent with susceptibility to dental caries in AD-HIES. Collectively, our findings illustrate a critical role for STAT3/Th17 in the containment of C. albicans as a commensal organism and an overall contribution in the establishment of fungal and bacterial oral commensal communities.

Authors

Loreto Abusleme, Patricia I. Diaz, Alexandra F. Freeman, Teresa Greenwell-Wild, Laurie Brenchley, Jigar V. Desai, Weng-Ian Ng, Steven M. Holland, Michail S. Lionakis, Julia A. Segre, Heidi H. Kong, Niki M. Moutsopoulos

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Figure 5

Increase in oral streptococci and dental caries susceptibility in AD-HIES.

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Increase in oral streptococci and dental caries susceptibility in AD-HIE...
(A) Differentially represented bacterial genera in actively infected (A_HIES, n = 9 for tongue and n = 8 for buccal samples) and uninfected (U_HIES, n = 9 for tongue and buccal samples) patients with AD-HIES, determined via LEfSe analysis. (B) Real-time PCR quantitation of the genus Streptococcus in tongue and buccal surfaces of HC and AD-HIES patients. The number of samples included in the tongue panel were HC n = 15, U_HIES n = 8, and A_HIES n = 8; for the buccal panel, number of samples were HC n = 15, U_HIES n = 7, and A_HIES n = 8. Streptococcus biomass values are expressed as log10 of 16S rRNA gene copy number. *P < 0.02 as determined by Kruskall-Wallis test and Dunn’s multiple comparisons test. (C) Differentially represented bacterial species found in actively infected and uninfected AD-HIES buccal samples, determined via LEfSe analyses. (D) Caries prevalence comparing HC (n = 22) and AD-HIES (n = 36) calculated using the Decayed, Missing, Filled Teeth (DMFT) index in dental radiographs. *P < 0.03 as determined by Mann-Whitney U test. (B and D) Boxes extend from the 25th to 75th percentiles, and the whiskers were plotted from the minimum to maximum value. All outlying values were shown.