PROJECT SUMMARY/ABSTRACT
The majority of deaths from cardiovascular disease (CVD) in US adults ages 25-54 years are associated
with suboptimal diet. While diet is an important target of CVD prevention efforts in adults, intervention on the
childhood diet may be more effective. Animal data suggest that early-life diet has the unique potential to modulate
biological systems and durably program a child’s biology for long-term health or disease. Yet, although NHLBI’s
Strategic Vision Objective 1 prioritizes understanding how diet modulates biological systems such as the micro-
biome and metabolome to sustain health, only limited animal and observational adult data exist. The objective
of this application is to define the molecular effects of a dietary pattern intervention on the gut microbiome and
circulating metabolome in young children. This objective will be attained through an ancillary study to a funded
clinical trial that tests the effects of a 12-month Dietary Approaches to Stop Hypertension (DASH) diet interven-
tion on adiposity and other CVH metrics (e.g., blood pressure, lipids) in 3- to 5-year old children (n=140). Using
additional participant samples, deep phenotyping and advanced bioinformatics, the proposed work will address
three specific aims. First, it will test the effect of the DASH diet intervention on the gut microbiome, including
abundances of microbial taxa, communities, and metabolism-related genes and transcripts. Second, it will define
the associations of diet and the gut microbiome with the circulating metabolome. Using targeted and nontargeted
metabolomics approaches, blood metabolites, metabolite networks, and metabolic pathways will be evaluated.
Finally, in an exploratory fashion, it will probe pathways linking the diet intervention with subsequent adiposity
and CVH metrics, through the gut microbiome and serum metabolome. The expected outcome is a preliminary
model of how the DASH diet alters the gut microbiome and circulating metabolome in young children, and how
these alterations relate to short-term CVH outcomes. These pilot data can be validated in larger samples, and
thereby contribute to eventual development of novel, targeted early-life dietary strategies to preserve ideal CVH.
The proposed research will also be leveraged as a training platform for Amanda Marma Perak, MD, who aims
to have an independent translational research program focused on understanding early-life determinants of CVH
and developing strategies to preserve life-long CVH. A team of prominent scientists will provide mentorship in a
rich research developmental environment at Northwestern University and Lurie Children’s Hospital. Customized
didactic, experiential, and professional development activities will complement mentored research experience to
ensure that Dr. Perak attains her short-term training goals to gain expertise in, first, systems biology molecular
methods and translation of mechanistic insights for clinical relevance, and second, clinical trials conduct. These
plans and resources will ensure that in 5 years, Dr. Perak is a molecular epidemiologist and pediatric cardiologist
who can lead multidisciplinary teams in translational research, taking new ideas through epidemiologic evalua-
tion, mechanistic study, and clinical application, with a sustained impact on the field of pediatric CVH promotion.
