The gastrointestinal tract harbors one of the highest densities of microorganisms on Earth. This collection of microbial genomes is an extension to the human genome, with clear implications on human health and disease. Early events in microbial colonization have a profound effect on physiology and immune education in the gut, thereby impacting disease susceptibility (including obesity, asthma, and other inflammatory disorders later in life). The human gut microbiota colonizes, stabilizes, and matures during the first few years of life, yet we know remarkably little about the natural history of how the microbiome forms in children. The study proposed here will provide fundamental knowledge about the newborn gut microbiome ? including its establishment; response to nutrients; and its implication for disease. This project aims to understand how maternal factors shape infant gut microbiome development and how early life microbial composition influence the allergy onset. Using newly established and future prospective birth cohorts, we will undertake metagenomic sequencing, strain-level analysis and bacterial isolation and characterization. (1) We will identify how delivery mode affects the abundant strains in the newborn gut, along with their potential parental sources. (2) We will isolate bacteria from newborn guts and determine if there is a personalized match between mother's breast milk and her child's gut microbiome. (3) We will examine the influence of the infant gut microbiome and early feeding on allergy to cow's milk. This research will illuminate how environmental factors modulate infant gut colonization and how the gut microbiota affect the onset of pediatric allergies. This will serve as a basis for the development of evidence- based interventions to colonize the gut of children born by C-section; supplement the diet of formula-fed children; and shift the infant gut microbiome to a less ?allergy-prone? state.

Public Health Relevance

This project seeks to transform our understanding of the infant gut microbiome ? the community of bacteria that live in our bodies and help educate our immune system, digest our food and protect us from pathogens. By analyzing samples from infants that will be collected at unprecedented scale and depth, we will examine (1) how delivery mode affects establishment of the infant gut microbiome; (2) how early life feeding impacts its development; and (3) the microbial community's implication on the onset of pediatric food allergies. This understanding will enable the development of evidence-based interventions to colonize the gut of children born by C-section, supplement the diet of formula-fed children, and shift the infant gut microbiome to a less ?allergy- prone? state.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Career Transition Award (K99)
Project #
5K99DK113224-02
Application #
9468378
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Saslowsky, David E
Project Start
2017-04-07
Project End
2019-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
Hall, Andrew Brantley; Yassour, Moran; Sauk, Jenny et al. (2017) A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med 9:103