Impact of gut microbiome composition on neuroendocrine signaling and feeding behavior in avoidant/restrictive food intake disorder

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT Avoidant/restrictive food intake disorder (ARFID) was recently added to DSM-5 and is common among adolescents and young adults. ARFID is characterized by restrictive eating defined by consuming an inadequate volume or variety of food. Most individuals with ARFID limit their diet to processed grains and dairy foods but avoid fruits, vegetables, and protein. The health consequences of ARFID include poor growth, low weight, vitamin and mineral deficiencies, and psychosocial impairment; however the pathophysiology remains totally unknown. Restricted dietary patterns have many consequences including altering the gut microbiota profile and levels of key appetite-regulating hormones that act as messengers between gut and brain. Conversely, the gut microbiota may contribute to persistent restrictive feeding behaviors by generating cravings for preferred foods or reducing overall food intake. Currently there are no studies that have examined the host microbiome in ARFID and its contribution to maladaptive feeding behaviors via neuroendocrine modulation. This proposal examines novel hypotheses by leveraging data from a funded R01 (MH108595), featuring measures of eating pathology, levels of appetite-regulating hormones, and stool microbiome composition. We will utilize an innovative, multi-disciplinary approach to examine the relationship between host microbiome, endocrine signaling, and feeding behaviors in ARFID. In both a cross-sectional and longitudinal analysis of individuals with ARFID and age-and sex-matched healthy controls, we propose to (1) characterize the gut microbiome in individuals with ARFID and healthy-weight controls, and (2) determine the predictive capacity of microbial phenotypes as potential biomarkers for changes in feeding behavior and improved diet variety among individuals with ARFID. Our findings will provide insight into the therapeutic potential of the microbiome and its contribution to disorder persistence or recovery. In collaboration with my co-sponsors (Drs. Lawson, Thomas, and Erdman) and expert collaborators (Drs. Alm, Eddy, and Misra), I have developed a comprehensive training plan that will prepare me with the requisite skill set for a research career investigating neurobiological and microbial mechanisms underlying aberrant feeding behaviors in patients with eating disorders. My F32 training and career development goals are to (1) enhance my knowledge of eating disorder pathophysiology, (2) cultivate skills in interpretation of neuroendocrine and microbiome data, and (3) provide a strong statistical, conceptual, and methodological foundation for submission of a K award application and further advance my research program and career.