Effects of estrus cycle stages on murine CDI severity

发情周期阶段对小鼠 CDI 严重程度的影响

• 批准号: 10625792
• 负责人: Ernesto V Abel-Santos
• 金额: $ 14.61万
• 依托单位: UNIVERSITY OF NEVADA LAS VEGAS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625792
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Animals; Antibiotics; Bacterial Infections; Biological; Biological Process; Biomedical Research; Blood; Body Temperature; Cells; Cessation of life; Clostridium difficile; Colitis; Colon; Contracts; Data; Data Analyses; Diagnosis; Diarrhea; Estradiol; Estrous Cycle; Estrus; Female; Germination; Goals; Gonadal Steroid Hormones; Grant; Health; Health Care Costs; Healthcare Systems; Hormonal; Hormonal Change; Hormones; Hospitals; Human; Immune system; Immunity; Immunologics; Incidence; Individual; Infection; Infection prevention; Inflammation; Intestines; Investigation; Knowledge; Male Castration; Metronidazole; Modeling; Molecular; Monitor; Multicenter Studies; Mus; Nosocomial Infections; Older Population; Organ Transplantation; Outcome; Patient Recruitments; Patient-Focused Outcomes; Patients; Phase; Population; Predisposition; Progesterone; Prophylactic treatment; Reporting; Reproduction spores; Research Personnel; Risk Factors; Serum; Severities; Sex Bias; Symptoms; Testing; Time; Tissues; Toxin; Training; Treatment Failure; Vancomycin; Virulence; Woman; Work; biosignature; chemotherapy; cohort; cost; cost estimate; experimental group; follow-up; graduate student; gut microbiota; high risk; high risk men; immunological status; individual patient; infection risk; male; men; microbiota; mortality; mouse model; novel strategies; prophylactic; public health relevance; response; screening; sex; sexual dimorphism; symptomatology; targeted treatment; undergraduate student

Abstract Clostridium difficile infection (CDI) is the main identifiable cause of antibiotic assoicated diarreah. The incidence of CDI is approximately 677/100,000 patients resulting in close to 500,000 cases annually in the US alone. CDI causes approximately 25,000 deaths a year and costs the health care system an estimated $6.3 billion/year. The main CDI risk factor is aggressive broad-spectrum antibiotic use. Similarly, older populations are more susceptible to CDI than younger cohorts. Conditions that reduce immunity (e.g. organ transplant, chemotherapy, AIDS) are also strongly correlated with CDI severity. Importantly, studies have shown that women have higher risk of CDI than men. CDI symptoms range from asymptomatic colonization to mild diarrhea to deathly colitis. All studies that delineate risk factors associated with CDI have been conducted with infected populations. Hence, the determinants of individual predisposition to contracting CDI are not well understood. Similarly, it is not clear why CDI symptoms severity vary among individual patients. Mice have been used successfully as a model to test novel approaches to treat for C. difficile infections. The murine CDI model present symptoms progression reminiscent of human CDI and respond to the same treatments. During our screening for CDI prophylactics, we observed that female mice developed more severe CDI signs compared to their male counterpart. In this application, we will test the hypothesis that sex hormone levels correlate with CDI symptom onset and severity. We will also determine whether sex-related variables affect CDI prevention and treatment. The data obtained in this project will allow determining the contribution of steroidal sex hormones and/or sexual status to murine CDI susceptibility. This information will then be used in a follow-up R01 application to determine the mechanisms underlying the differences between male and female CDI susceptibility.

摘要 艰难梭菌感染（CDI）是抗生素相关性腹泻的主要原因。的 CDI的发生率约为677/100，000例患者，导致美国每年近500，000例病例 一个人CDI每年造成约25，000人死亡，估计医疗保健系统的成本为6.3美元 亿元/年。 CDI的主要危险因素是积极使用广谱抗生素。同样，老年人 比年轻人更容易患CDI。降低免疫力的疾病（例如器官移植， 化疗、AIDS）也与CDI严重程度强烈相关。重要的是，研究表明， 女性患CDI的风险高于男性。 CDI症状范围从无症状定植到轻度腹泻到死亡性结肠炎。的所有研究 描述与CDI相关的危险因素已经在感染人群中进行。所以 个体易患CDI的决定因素尚不清楚。同样， 为什么CDI症状的严重程度在个体患者之间存在差异。 小鼠已成功地用作测试治疗C.艰难感染。 鼠CDI模型呈现出令人联想到人CDI的症状进展，并对相同的CDI反应。 治疗。在我们筛选CDI趋化剂的过程中，我们观察到雌性小鼠发展得更严重， 与男性相比，CDI标志。 在本申请中，我们将检验性激素水平与CDI症状相关的假设 发作和严重程度。我们还将确定性相关变量是否影响CDI的预防和治疗。 本项目获得的数据将允许确定类固醇性激素的贡献 和/或性状态对鼠CDI易感性的影响。该信息随后将用于后续R 01 应用，以确定男性和女性CDI之间差异的机制 易感性