Impact of pet contact on antimicrobial-associated dysbiosis and Clostridioides difficile infection

宠物接触对抗菌药物相关生态失调和艰难梭菌感染的影响

• 批准号: 10589116
• 负责人: Laurel Elizabeth Redding
• 金额: $ 17.93万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-09 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589116
• 关键词: Age Years; Animals; Asthma; Bioinformatics; Cessation of life; Characteristics; Clinical; Clostridium difficile; Communities; Data; Dedications; Dental Implants; Development; Development Plans; Diarrhea; Disease; Ecology; Elderly; Environment; Epidemiology; Foundations; Future; Health; Healthcare; Human Microbiome; Indigenous; Infection; Infectious Disease Epidemiology; Intervention; Longitudinal cohort study; Mentors; Metabolic; Methods; Microbiology; Morbidity - disease rate; Outcome; Ownership; Patients; Pennsylvania; Persons; Physical activity; Proliferating; Pseudomembranous Colitis; Recovery; Recurrence; Research; Research Personnel; Research Proposals; Risk; Sampling; Source; Testing; Therapeutic; Therapeutic Intervention; Training; University resources; antimicrobial; atopy; career; career development; colonization resistance; deep sequencing; dysbiosis; experience; fecal transplantation; functional restoration; gut dysbiosis; gut microbiome; gut microbiota; improved; microbial; microbiome; microbiome composition; microbiome research; microbiota; mortality; novel; older patient; pathogen; pathogenic bacteria; patient oriented research; pet animal; prevent; prophylactic; prospective; protective effect; restoration; statistics; stress reduction; success; user-friendly

PROJECT SUMMARY Clostridioides difficile infection (CDI) is one of the most common causes of healthcare-associated infectious diarrhea and results in significant morbidity and mortality. CDI occurs when the native gut microbiome is disrupted, most often following antimicrobial therapy, and the consequent dysbiosis results in a decrease in microbial diversity, changes in abundance of certain bacterial taxa, and loss of colonization resistance against C. difficile. Restoration of a “functionally intact” gut microbiome is critical to clearing C. difficile, and inadequate restoration can lead to recurrent CDI. The recovery of the gut microbiome from dysbiosis is poorly understood, and factors associated with having and re-gaining a microbiome capable of providing colonization resistance against C. difficile are not well known. While animal reservoirs can serve as potential sources of pathogenic bacteria, studies by the candidate and other investigators found that pet ownership protects against colonization and re-infection with C. difficile. Moreover, microbiota are shared between pets and their owners, and the microbiomes of pets contain bacterial taxa that provide colonization resistance against C. difficile. Based on these data, the proposed research will 1) test the hypothesis that the observed protective effects of pet ownership are due to sharing of microbiota that provide colonization resistance against C. difficile between pets and owners; 2) determine whether pet contact mitigates antimicrobial-associated disruption of the gut microbiome and enhances its recovery; and 3) assess whether pet contact decreases the likelihood of colonization and infection with C. difficile following antimicrobial therapy. This will be accomplished though longitudinal sampling of the gut microbiome within the patient/pet unit among patients older than 60 years (i.e., at greatest risk of CDI) receiving prophylactic antimicrobials for non-enteric indications (dental implants). The study will further define epidemiologic and pathophysiologic characteristics of CDI that could enhance therapeutic options for this disease. The underlying premise that animals are a source of protective microbiota rather than a reservoir of C. difficile represents a paradigm shift in CDI epidemiology that may identify animal contact as a novel microbiome-based form of therapy. The proposed study will form a foundation for an independent career in patient-oriented research dedicated to understanding and mitigating antimicrobial-associated dysbiosis and CDI. The candidate will acquire experience in directing a large, observational microbiome study and essential training in the advanced statistical and bioinformatics methods necessary to analyze the interaction between patient-level factors and microbial ecology. The research proposal is paired with a career development plan that makes use of the extensive resources of the University of Pennsylvania and that capitalizes on a superlative mentoring committee with broad, complementary expertise in infectious diseases epidemiology, deep sequencing methods, bioinformatics, and microbiology.

项目摘要 艰难梭菌感染（CDI）是医疗保健相关性疾病最常见的原因之一。 感染性腹泻并导致显著的发病率和死亡率。CDI发生时， 微生物组被破坏，最常见的是在抗微生物治疗后，随后的生态失调导致 微生物多样性的减少，某些细菌类群丰度的变化，以及定植的丧失 对C.很难恢复“功能完整”的肠道微生物组对于清除C。 困难，修复不充分可导致复发性CDI。肠道微生物组的恢复， 生态失调的理解很少，与拥有和重新获得能够 提供对C.困难并不为人所知。虽然动物储库可以作为 潜在的致病菌来源，候选人和其他调查人员的研究发现，宠物 所有权可以防止C.很难此外，微生物群是共享的 宠物和它们的主人之间的关系，宠物的微生物组包含细菌分类群， 对C.很难基于这些数据，拟议的研究将1）测试假设， 观察到的宠物所有权的保护作用是由于共享微生物群， 对C.宠物和主人之间的困难; 2）确定宠物接触是否减轻 抗微生物剂相关的肠道微生物组破坏并增强其恢复;以及3）评估是否 宠物接触降低了C.抗菌药物治疗后出现困难 疗法这将通过对患者/宠物体内的肠道微生物组进行纵向采样来实现 60岁以上患者的单位（即，CDI风险最大）接受预防性抗菌药物， 非肠道适应症（牙科植入物）。 这项研究将进一步确定CDI的流行病学和病理生理学特征， 增强对这种疾病的治疗选择。动物是一种保护性资源的基本前提 微生物群而不是C. difficile代表了CDI流行病学的范式转变， 确定动物接触是一种新的基于微生物组的治疗形式。拟议的研究将形成一个 基金会为一个独立的职业生涯，在病人为导向的研究，致力于了解和减轻 抗生素相关的生态失调和CDI。候选人将获得导演大型， 观察性微生物组研究和先进统计和生物信息学方法的基本培训 有必要分析患者层面因素与微生物生态学之间的相互作用。研究 该提案与利用大学广泛资源的职业发展计划相结合 宾夕法尼亚州，并利用了一个最高级的指导委员会， 传染病流行病学、深度测序方法、生物信息学和微生物学方面的专业知识。