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Technology for Longitudinal Whole-Genome Characterization of Term and Pre-Term Breast Milk Microbiomes

Award Number: R21HD118464
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Technology for Longitudinal Whole-Genome Characterization of Term and Pre-Term Breast Milk Microbiomes - ABSTRACT: Breast milk is essential for infant nutrition and immune system development, yet its microbiome remains poorly understood due to significant technical barriers. Currently, genome-level analyses are challenging because the human DNA in breast milk can overwhelm microbial DNA by ratios as high as 99.9% to 0.1%. Additionally, contamination from laboratory procedures has hindered reproducibility and limited confidence in microbial identification from breast milk. In this project, we aim to overcome these limitations by developing and rigorously validating a novel microbial enrichment and metagenomic sequencing method (MEM technology) specifically designed for quantitative characterization of the complete genomes of bacteria, archaea, and fungi directly from breast milk samples. Our overall objective is to produce definitive, genome-level data on the breast milk microbiome and its interactions with the infant gut microbiome. We will achieve this objective through two Specific Aims: Aim 1: Develop and validate MEM technology for rigorous, quantitative genome-level microbial analyses directly from breast milk samples. We will optimize MEM using defined microbial communities and cultured isolates from human milk, ensuring robust differentiation between genuine microbial signals and laboratory contaminants. Aim 2: Demonstrate and apply MEM technology to longitudinally collected, paired samples from two pilot cohorts: a) Healthy full-term mother-infant dyads (paired breast milk, maternal stool, infant stool samples), b) Pre-term mother-infant dyads (paired breast milk and infant stool samples). This research will produce two novel datasets: the first-ever MAG-based, longitudinal datasets from paired mother-infant samples, clarifying the stability of the breast milk microbiome over time and investigating potential microbial transmission pathways (colonization, persistence, elimination). Understanding these microbial dynamics is critical because early gut microbiome colonization profoundly impacts infant immune maturation and susceptibility to dysbiosis-related conditions such as allergies, metabolic disorders, and necrotizing enterocolitis (NEC). Ultimately, this validated MEM technology and associated pilot datasets will provide essential tools and foundational knowledge that enable future microbiome-based interventions, such as identifying probiotic strains for clinical use, predicting microbial risk factors for diseases like maternal mastitis or neonatal sepsis, and clarifying microbial transmission pathways. This project represents a significant advancement in maternal-infant microbiome research, directly impacting public health by providing knowledge crucial for improving infant health outcomes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $467,500 )
2026	2026	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	8/18/2026	NEW	$467,500
														Subtotal = $467,500

Grand Total All Awards = $467,500

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Technology for Longitudinal Whole-Genome Characterization of Term and Pre-Term Breast Milk Microbiomes

Award Number: R21HD118464

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/18/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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