Investigating the effects of psychosocial stress on laryngeal microbiology and epithelial barrier integrity

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ABSTRACT Biological mechanisms underlying psychosocial stress-induced changes to the larynx remain understudied. Psychological stress symptomology is concurrently reported in 25% of patients with voice problems. From a biological perspective, psychosocial stress can have deleterious consequences on both microbial communities and epithelial barrier integrity, as reported, in other mucosal organs such as the gut and stomach. First, the laryngeal microbiome has a distinct microbial composition when compared to the gut. How this distinct composition is influenced by psychosocial stress remains unknown. Independently, stress-induced changes to epithelial permeability (such as reduced epithelial proliferation and reduced mucus thickness) may potentially leave the larynx susceptible to further infection. This proposal broadly questions whether psychosocial stress can lead to microbial dysbiosis and compromised epithelial barrier integrity. In our proposed experiments, mice will be assigned to unstressed or stressed groups. Psychosocial stress will be induced via a validated chronic restraint stress protocol. Specific Aim 1 will determine laryngeal microbial adaptations following chronic, psychosocial stress exposure. We hypothesize that psychosocial stress will result in reduced microbial diversity and abundance, altered composition and differential abundance of specific bacterial taxa, and distinct predicted functional profiles in the laryngeal microbiota. To obtain laryngeal microbiota outcomes, 16s rRNA sequencing will be used completed on bacteria extracted from murine laryngeal tissue. Specific Aim 2 will delineate changes in vocal fold epithelial integrity post-chronic psychosocial stress. We hypothesize that psychosocial stress will result in increased bacterial translocation, decreased mucus thickness, reduced epithelial proliferation, reduced epithelial cell junction integrity, and altered gene expression of mucins in the vocal folds. Immunohistochemistry/ Immunofluorescence and qPCR will be used to delineate consequences of psychosocial stress on the laryngeal epithelium. Taken together, we hypothesize that psychosocial stress will concomitantly lead to microbial dysbiosis and alter epithelial barrier integrity in the larynx. Data from these two aims will lay the groundwork for identifying and manipulating specific bacterial phyla to delineate host-microbial epithelial interactions of psychosocial stress in the larynx.