The Oral Mucosal Microbiome in patients with Impaired Th17 Differentiation

Objectives: Th17 cells play a critical role in mucosal host defense against extracellular bacteria and fungi. Primary immune deficient patients with autosomal dominant hyper-IgE syndrome (AD-HIES) harbor STAT3 mutations, leading to defective cytokine signaling and differentiation of Th17 cells. These patients are predisposed to various infections, including mucocutaneous candidiasis. In this rare patient cohort, we evaluated susceptibility to oral disease, and then characterized bacterial and fungal oral mucosal microbiomes.
Methods: 6 patients diagnosed with AD-HIES and 6 healthy volunteers were included in our study. Detailed oral examination was performed and samples were collected from oral mucosal surfaces according to the Human Microbiome Project protocol. Following DNA isolation, samples were subjected to 454-pyrosequencing of 16S rRNA and ITS1 gene libraries, to describe bacterial and fungal microbiomes, respectively.
Results: Medical history and clinical examination revealed that all AD-HIES patients had susceptibility to oral candidiasis with 4 out of 6 patients presenting with active lesions at the time of sampling. Bacterial microbiome analyses demonstrated that AD-HIES communities exhibit decreased richness and diversity as compared to healthy communities, and clustered separately from healthy controls when using community membership and structure metrics. We found a few oral commensal bacterial species overrepresented in the AD-HIES patients but most prominently a large depletion of health-associated taxa. The fungal microbiome also showed reduced diversity compared to healthy subjects, with a clear predominance of opportunistic fungi Candida species in AD-HIES, particularly in patients with active mucosal lesions.
Conclusions: AD-HIES oral mucosal microbiome has a distinct composition and structure, harboring less diversity than health-associated microbial communities. Future studies will be aimed towards understanding how the interplay between dysbiotic bacterial and fungal communities may be contributing to increased fungal susceptibility.