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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Categories: 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 1

Oral mucosal mycobiome in AD-HIES differs significantly from healthy controls.

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Oral mucosal mycobiome in AD-HIES differs significantly from healthy con...
(A) Principal coordinates analysis (PCoA) plot analyzing community structure (based on θ YC distances), showing that fungal communities of patients with autosomal dominant hyper-IgE syndrome (AD-HIES) cluster apart from healthy controls (HC) in tongue and buccal surfaces. P < 0.001 as determined by AMOVA comparing HC versus all AD-HIES combined. P < 0.001 as determined by AMOVA comparing actively infected (A_HIES, dark purple) and uninfected (U_HIES, light purple) AD-HIES patients. Each circle represents 1 sample. Some data points are not visible, as they get superimposed due to tight clustering. (B) Nonparametric Shannon diversity index of tongue and buccal fungal communities of HC, U_HIES, and A_HIES patient samples. ****P < 0.0001 as determined by Kruskall-Wallis test and Dunn’s multiple comparisons test. (C) Number of observed fungal genera in tongue and buccal communities of HC, U_HIES, and A_HIES patient samples. ****P < 0.0001 and *P < 0.01 as determined by Kruskall-Wallis test and Dunn’s multiple comparisons test. (A–C) The number of samples per group included in these graphs for HC were n = 23 for tongue and n = 25 for buccal, and n = 9 for tongue and n = 8 for buccal for both U_HIES and A_HIES patient groups. Boxes extend from the 25th to 75th percentiles, and the whiskers were plotted from the minimum to maximum value. All outlying values were shown.