PROJECT 3 ABSTRACT Diarrheal disease remains a leading cause of childhood illness and mortality worldwide and is especially life threatening in infants and children under 5 years when the immune system is developing. The gut microbiome begins its development during this same critical window, and its interaction with adaptive and innate immunity is required to achieve immune competence. Although vaccines have helped to reduce the population burden of gastrointestinal infections, the magnitude of individual-level protection conferred by immunization varies between children. This project seeks to test the hypothesis that the structure of bacterial communities residing in the gut may be an important ? and potentially modifiable ? factor influencing infants' abilities to mount a beneficial immune response to vaccines and disease risk. We will leverage data from the unique, prospective New Hampshire Birth Cohort Study (2009 to present) that collects detailed epidemiological (e.g., gestational age, delivery mode, medical records, antibiotic exposures, infections), lifestyle (e.g., maternal diet, smoking, probiotic intake, infant feeding practices), and biospecimen (e.g., maternal peripheral blood, cord blood, stool samples) from maternal-child dyads recruited during pregnancy and followed through the early childhood period. The preliminary clinical endpoints to be investigated include infants' rotavirus mucosal antibody concentrations in stool samples and gastroenteritis occurrence during the first year of life.
In Aim 1, we will examine the associations of putative disruptors of the early life microbiome assembly (i.e. cesarean deliveries, antibiotics, and formula feeding) and infant vaccine response and gastroenteritis risks.
In Aim 2, we will compare how the community structure, alpha-diversity level, and relative abundance of specific bacterial taxa in the intestinal microbiome relate to infant vaccine response and gastroenteritis risks.
In Aim 3, we will implement a novel approach for investigating the role of microbiome in mediating associations between perinatal and early postnatal exposures and infant's and mucosal antibody response and risk of gastroenteritis. Determining the role of the infant gut microbiome and the factors that influence the microbiome in immunogenic vaccine responses will help us to identify key elements of microbial colonization patterns in relationship to immune training in infants, as well as identify targets for interventions designed to promote vaccine effectiveness and reduce the burden of infant infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM104416-08
Application #
9843722
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
8
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Romano, Megan E; Eliot, Melissa N; Zoeller, R Thomas et al. (2018) Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study. Int J Hyg Environ Health 221:623-631
Everson, Todd M; Punshon, Tracy; Jackson, Brian P et al. (2018) Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts. Environ Health Perspect 126:017010
Emond, Jennifer A; Karagas, Margaret R; Baker, Emily R et al. (2018) Better Diet Quality during Pregnancy Is Associated with a Reduced Likelihood of an Infant Born Small for Gestational Age: An Analysis of the Prospective New Hampshire Birth Cohort Study. J Nutr 148:22-30
Nachman, Keeve E; Punshon, Tracy; Rardin, Laurie et al. (2018) Opportunities and Challenges for Dietary Arsenic Intervention. Environ Health Perspect 126:84503
Moen, Erika L; Bynum, Julie P; Austin, Andrea M et al. (2018) Assessing Variation in Implantable Cardioverter Defibrillator Therapy Guideline Adherence With Physician and Hospital Patient-sharing Networks. Med Care 56:350-357
Braun, Joseph M; Chen, Aimin; Hoofnagle, Andrew et al. (2018) Associations of early life urinary triclosan concentrations with maternal, neonatal, and child thyroid hormone levels. Horm Behav 101:77-84
Punshon, Tracy; Jackson, Brian P (2018) Essential micronutrient and toxic trace element concentrations in gluten containing and gluten-free foods. Food Chem 252:258-264
El-Jawahri, Areej; Fishman, Sarah R; Vanderklish, Julie et al. (2018) Pilot study of a multimodal intervention to enhance sexual function in survivors of hematopoietic stem cell transplantation. Cancer 124:2438-2446
El-Jawahri, Areej; Nelson-Lowe, Margaret; VanDusen, Harry et al. (2018) Patient-Clinician Discordance in Perceptions of Treatment Risks and Benefits in Older Patients with Acute Myeloid Leukemia. Oncologist :
Cai, Yunliang; Wu, Shaoju; Zhao, Wei et al. (2018) Concussion classification via deep learning using whole-brain white matter fiber strains. PLoS One 13:e0197992

Showing the most recent 10 out of 131 publications