Early Life Experience Imprints Gut Microbiome in Preterm Infants

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Abstract The candidate, Xiaomei Cong, PhD, RN, proposes a Mentored Patient-Oriented Research Career Development Award project to enhance her ability to achieve her goal of becoming an independent clinical investigator who will lead the field of infant stress and pain. With preterm birth substantial gains in survival, concerns have focused on significant increases in neurological morbidity and long-term adverse outcomes related to the immature neuro-immune systems and stressful early life experience in the neonatal intensive care (NICU) stay. However, how the mechanisms of early life stress alter infant neurodevelopment remains largely unknown. To continue progress towards her goal, the candidate will examine the new models of brain- gut-microbiota signaling mechanism involved in early life stress and prediction of infant neurodevelopment using cutting-edge microbiological analysis (i.e., gut microbiome) and immune-inflammatory biomarker prediction strategies (i.e., fecal cytokines and calprotectin). Three specific research aims are proposed in a prospective longitudinal study to examine: (1) preterm infants' gut microbiome patterns and mucosal immune- inflammatory responses over the first 3 weeks of NICU stay; (2) the linkage of gut microbiome patterns and mucosal immune-inflammatory responses with early life stress; and (3) the linkage of gut microbiome and mucosal immune-inflammatory responses with autonomic nervous and neurobehavioral outcomes. The candidate's previous training and research experience provided her skills to plan, implement, and analyze data from clinical experimental studies in infant stress/pain. Progress toward the career goals requires her to develop expertise in additional content areas including knowledge and technology of brain-gut signaling mechanism and genomic approaches to microbiome analysis. An expert interdisciplinary mentor advisory committee has been selected and the candidate will gain knowledge by hands-on experience of: (1) microbiome and genomics knowledge and technology by Drs. Graf and Gregory; (2) mechanism of brain-gut signaling involved in infant stress by Drs. Henderson and Hussain; (3) biostatistics and informatics by Drs. Walsh and Graf; and (4) dissemination and grant writing by all mentors. Training and mentoring activities will include formal coursework, learning modules, mentored training, workshops, and other professional activities. The project addresses a high priority of the NINR strategic plan of disease prevention and quality of life improvement and also a priority of NIH specified by a recent initiative, the "Human Microbiome Project." The award will enable 75% of her academic time to be devoted to research and training. The candidate will work with mentors in a world-class research environment and successfully reach her goals. Study results will provide the preliminary data for an R01 grant proposal and will further contribute to neonatal care in reducing negative consequences of stress in high-risk infants. .