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.

项目概要 拟议的临床和转化研究领域的 K23 职业发展奖将为 Dr. 奠定基础。 刘媛将成为一名独立的临床医生科学家，拥有严重儿童早期龋齿 (S-ECC) 方面的专业知识。 K23 培训目标按顺序进行，并将支持她发展关键专业知识 在三个领域：1）发展设计和进行临床研究的高级技能； 2）获得先进的 真菌生物学和微生物组的知识和方法； 3) 改善科学交流、资助写作 技能和网络。候选人将获得指导纵向学习和基本培训的经验 通过利用宾夕法尼亚大学的广泛资源并利用 跨学科指导委员会在临床研究、流行病学、 生物工程、微生物组和生物信息学。 S-ECC 是一个重大的公共卫生问题，其特征是 失调的口腔微生物负担导致幼儿牙齿上形成持久且有毒的生物膜，从而导致 蛀牙猖獗。这个过程不仅会破坏牙列，还会对牙齿产生负面影响。 总体健康状况，例如复杂的全身感染，以及幼儿的福祉。新兴临床 有证据表明白色念珠菌在 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，鹅口疮 12 个月以下幼儿中（口咽念珠菌病或 OPC）的检测呈密切相关 不久之后，特别是在 13 至 36 个月之间，就会出现龋齿。然而，只有跨 迄今为止已经进行了部分人体研究。有必要进行纵向研究以更好地评估 幼儿 OPC 和 S-ECC 之间的因果关系。与此同时，还需要进一步研究来确定 真菌在龋齿中的作用以及口腔中念珠菌定植是否可以作为 S-ECC 风险的可靠临床标志物。 为了解决这个问题，拟议的研究将侧重于进行为期 2 年的前瞻性纵向研究 研究早期 OPC 与 S-ECC 进展之间的关联以及念珠菌的影响 对功能斑块微生物组和生物膜毒力的定植。刘博士将研究3个具体目标： (1) 检查一组婴儿中早期 OPC 和 S-ECC 发育之间的关联； (2) 评估 OPC 和念珠菌定植对婴儿菌斑微生物组的影响； (3)研究念珠菌的作用 生物膜致龋特性。这项临床和转化工作的结果将进一步阐明因果关系 OPC 和 S-ECC 之间的联系，并增强对真菌对发病机制贡献的理解 S-ECC 的。总的来说，这些结果将为机械临床研究和 制定预防 S-ECC 的针对性策略。这个K23奖项将为刘博士提供新的知识 作为临床医生科学家的职业目标至关重要的领域，实施拟议的研究计划并建立 一项独立研究计划，目标是在 K23 奖项结束之前获得 R01。