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

研究社会心理压力对喉部微生物学和上皮屏障完整性的影响

• 批准号: 10824680
• 负责人: ANUMITHA VENKATRAMAN
• 金额: $ 7.08万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10824680
• 关键词: 16S ribosomal RNA sequencing; Acoustics; Aerobic; Bacteria; Bacterial Translocation; Biological; Biology; Brain; Chronic; Collection; Data; Development; Down-Regulation; Epithelial Cell Junction; Epithelium; Exhibits; Exposure to; Fellowship; Fluorescent in Situ Hybridization; Functional disorder; Future; Gene Expression; Genes; Immunofluorescence Immunologic; Immunohistochemistry; Infection; Knowledge; Laryngeal Epithelium; Larynx; Lead; Link; Mediating; Membrane; Methodology; Microbe; Microbiology; Mucins; Mucous Membrane; Mucous body substance; Mus; National Research Service Awards; Organ; Outcome; Pathology; Patients; Periodicals; Permeability; Personality Traits; Polymerase Chain Reaction; Predisposition; Probiotics; Proliferating; Protocols documentation; Psychological Stress; Psychosocial Influences; Psychosocial Stress; Reporting; Research; Role; Sampling; Social Behavior; Stains; Stomach; Stress; Stressful Event; Therapeutic Intervention; Thick; Time; Tissues; Treatment/Psychosocial Effects; Voice; Voice Disorders; biological adaptation to stress; dysbiosis; experimental study; gut microbiota; injury recovery; mechanical stimulus; microbial; microbial community; microbial composition; microbial host; microbiome; microbiota; mouse model; mucosal microbiota; pathogenic bacteria; probiotic therapy; response; restraint stress; sex; skills; targeted treatment; vocal cord

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.

抽象的 社会心理压力引起的喉部变化的生物学机制仍未得到充分研究。 25% 有声音问题的患者同时报告有心理压力症状。来自一个 从生物学角度来看，社会心理压力会对微生物群落产生有害后果 据报道，在肠道和胃等其他粘膜器官中，上皮屏障的完整性也受到影响。首先， 与肠道相比，喉部微生物组具有独特的微生物组成。这是如何截然不同的 成分是否受到心理社会压力的影响仍然未知。独立地，压力引起的变化 上皮通透性（例如上皮增殖减少和粘液厚度减少）可能会 使喉部容易受到进一步感染。该提案广泛质疑社会心理压力是否 可导致微生物失调和上皮屏障完整性受损。在我们提出的实验中，小鼠 将被分配到无压力或有压力的组。心理社会压力将通过经过验证的慢性诱发 约束应激协议。具体目标 1 将确定慢性、 心理社会压力暴露。我们假设社会心理压力会导致微生物减少 多样性和丰度、特定细菌类群的组成和差异丰度的改变以及独特的 预测喉部微生物群的功能特征。为了获得喉部微生物群结果，16s rRNA 测序将用于从小鼠喉组织中提取的细菌。具体目标 2 将 描绘慢性心理社会压力后声带上皮完整性的变化。我们假设 心理社会压力会导致细菌易位增加、粘液厚度减少、 上皮增殖、上皮细胞连接完整性降低以及粘蛋白基因表达改变 声带。免疫组织化学/免疫荧光和 qPCR 将用于描述以下后果： 对喉上皮的心理社会压力。综上所述，我们假设社会心理压力会 同时导致微生物失调并改变喉上皮屏障的完整性。这两个数据 目标将为识别和操纵特定细菌门以描绘宿主微生物奠定基础 喉部心理社会压力的上皮相互作用。