Association between early Candida infection (oral thrush) and severe early childhood caries

早期念珠菌感染（鹅口疮）与严重儿童早期龋齿之间的关联

• 批准号: 10739505
• 负责人: Yuan Liu
• 金额: $ 16.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739505
• 关键词: Address; Affect; Age; Age Months; Ambulatory Care; American; Applications Grants; Area; Bioinformatics; Biology; Biomedical Engineering; Biometry; Candida; Candida albicans; Child; Childhood; Chronic; Clinical; Clinical Markers; Clinical Research; Collaborations; Communicable Diseases; Communication; Computer Analysis; Databases; Dental Enamel; Dental Plaque; Dental caries; Dentition; Detection; Development; Diet Habits; Disease; Early Intervention; Economics; Electronic Health Record; Epidemiology; Experimental Models; Exposure to; Family; Foundations; Future; Goals; Grant; Hardness; Health; Healthcare Systems; Human; Image; Infant; Infection; K-Series Research Career Programs; Knowledge; Left; Life; Link; Longitudinal Studies; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic Pathway; Methods; Microbial Biofilms; Microradiography; Odontogenesis; Oral; Oral candidiasis; Oral cavity; Pain; Pathogenesis; Pediatric Hospitals; Pennsylvania; Personal Satisfaction; Philadelphia; Play; Preventive; Preventive therapy; Process; Property; Public Health; Recording of previous events; Research; Resources; Retrospective Studies; Risk; Risk Factors; Risk Marker; Role; Sampling; Scientist; Severities; Shotguns; Structure; Surface; Systemic infection; Techniques; Testing; Therapeutic; Toddler; Tooth structure; Training; Translational Research; Underserved Population; Universities; Virulence; Virulent; Visit; Writing; career; cariogenic bacteria; cohort; deciduous tooth; demineralization; dental biofilm; design; dysbiosis; early childhood; experience; follow-up; fungus; improved; infancy; longitudinal, prospective study; low and middle-income countries; metagenomic sequencing; microbial; microbial community; microbial composition; microbiome; microbiota; novel; oropharyngeal thrush; prevent; programs; sex; skills; social; spatiotemporal; sugar; tooth surface

PROJECT SUMMARY The proposed K23 career development award in clinical and translational research will form a foundation for Dr. Yuan Liu to become an independent clinician-scientist, with expertise on severe early childhood caries (S-ECC). The K23 training objectives progress in a sequential fashion and will support her development of key expertise in 3 areas: 1) developing advanced skills in designing and conducting clinical studies; 2) acquiring advanced knowledge and methods in fungal biology and microbiome; 3) improving scientific communication, grant writing skills and networking. The candidate will acquire experience in directing longitudinal study and essential training by making the use of the extensive resources at the University of Pennsylvania and capitalizing on an interdisciplinary mentoring committee with broad, complementary expertise in clinical research, epidemiology, bioengineering, microbiome, and bioinformatics. S-ECC is a major public health problem characterized by dysbiotic oral microbial burden leading to a persistent and virulent biofilm on the teeth of toddlers that causes rampant tooth decay. This process not only destroys the dentition but can also have a negative impact on the general health, such as complicated systemic infections, and the well-being of young children. Emerging clinical evidence has spotlighted the potential role of Candida albicans in S-ECC. Furthermore, our retrospective study using electronic health records (EHR) from six major children’s hospitals revealed that, oral thrush (oropharyngeal candidiasis or OPC) detection in toddlers less than 12 months of age was strongly associated with the development of dental caries soon after, particularly between 13 and 36 months. However, only cross- sectional human studies have been performed thus far. Longitudinal studies are warranted to better assess the causal association between OPC and S-ECC in toddlers. In parallel, further studies are needed to determine the fungal role in caries and if Candida colonization in oral cavity could be a reliable clinical marker for risk of S-ECC. To address this, the proposed research will be focused on conducting a 2-year prospective longitudinal study to investigate the association between early OPC and the progression of S-ECC, and the impact of Candida colonization on the functional plaque microbiome and biofilm virulence. Dr. Liu will investigate 3 specific aims: (1) examine the association between early OPC and S-ECC development in a cohort of infants; (2) evaluate the influence of OPC and Candida colonization on the plaque microbiome in infants; (3) study the role of Candida on biofilm cariogenic properties. Results from this clinical and translational effort will further elucidate the causal link between OPC and S-ECC, and enhance the understanding of fungal contributions to the etiopathogenesis of S-ECC. Collectively, these results will provide future opportunities for mechanistic clinical studies and developing targeted strategies for preventing S-ECC. This K23 award will provide Dr. Liu with new knowledge in the areas essential to her career goals as a clinician-scientist, implement the proposed research plan and build an independent research program with the goal of receiving an R01 prior to the end of the K23 award.

项目摘要 拟议的K23临床和翻译研究职业发展奖将为Dr. 刘人将成为独立的临床科学家，拥有严重的幼儿汽车（S-ECC）专业知识。 K23培训目标以顺序发展，并将支持她的主要专业知识的发展 在3个领域：1）在设计和进行临床研究方面发展高级技能； 2）先进 真菌生物学和微生物组的知识和方法； 3）改善科学沟通，赠款写作 技能和网络。候选人将获得指导纵向研究和基本培训的经验 通过在宾夕法尼亚大学使用大量资源并利用 跨学科指导委员会在流行病学临床研究方面拥有广泛，完整的专业知识， 生物工程，微生物组和生物信息学。 S-ECC是一个主要的公共卫生问题 不植物的口服微生物燃烧，导致幼儿的牙齿持续毒性生物膜 渐变的蛀牙。这个过程不仅破坏了牙列，而且还会对 一般健康，例如复杂的全身感染和幼儿的福祉。新兴临床 证据焦点介绍了白色念珠菌在S-ECC中的潜在作用。此外，我们的回顾性研究 使用六家主要儿童医院的电子健康记录（EHR）显示，口腔鹅口疮 （口咽念珠菌病或OPC）在不到12个月大的幼儿中检测是密切相关的 随着龋齿的发展，不久之后，尤其是在13到36个月之间。但是，只有交叉 到目前为止，已经进行了人类研究。有必要更好地评估纵向研究 幼儿中OPC与S-ECC之间的因果关系。同时，需要进一步的研究来确定 真菌在携带中的作用以及口腔中的念珠菌定殖是否可能是S-ECC风险的可靠临床标记。 为了解决这个问题，拟议的研究将集中于进行为期2年的前瞻性纵向研究 研究早期OPC与S-ECC的进展与念珠菌的影响之间的关联 功能性斑块微生物组和生物膜病毒的定殖。刘博士将调查3个具体目标： （1）检查一群婴儿的早期OPC与S-ECC发育之间的关联； （2）评估 OPC和念珠菌定殖对婴儿斑块微生物组的影响； （3）研究念珠菌的作用 在生物膜的富特性上。这项临床和翻译工作的结果将进一步阐明因果关系 OPC和S-ECC之间的联系，并增强对真菌对疗法发生的贡献的理解 S-ECC。这些结果共同为机械临床研究提供了未来的机会， 制定有针对性的防止S-ECC的策略。该K23奖将为Liu博士提供新知识 她作为临床科学家职业目标至关重要的领域，实施拟议的研究计划并建立 一个独立的研究计划，目的是在K23奖励结束之前获得R01。