P50HD106463

Optimization of Antibiotics in Mothers and Their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses - Project Summary

The UC San Diego MPRINT CET, entitled "Optimization of Antibiotics in Mothers and Their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses," brings together a team of highly experienced and proven collaborative investigators with leadership roles in maternal and pediatric clinical pharmacology, fundamental research methods, and technologies.

Across its highly integrated and synergistic components, the UCSD MPRINT CET addresses critical barriers in maternal-infant pharmacology regarding:

1. The pharmacokinetics of infant exposure to maternal antibiotic treatment via breastmilk or close contact.
2. The impact of maternal antibiotic therapy or prophylaxis on the establishment of the normal infant microbiome and gut metabolome.
3. Potential downstream effects of such antibiotic exposure on infant immune function and hepatic cytochrome P450 drug metabolizing enzymes.
4. The pivotal role of breast milk both as a conduit for antibiotic transfer and a source of beneficial human/mammalian milk oligosaccharides (HMOS/MMOS) that may support microbiome and immune integrity in the face of antibiotic stress.

The successful operation and outcome of our MPRINT CET is accomplished through three projects (clinical, basic science, and data science), an administrative core, and two technology cores: the Milk Analytics Core (MAC) and Pharmacometrics and Analytical Chemistry Core (PACC).

In the clinical project, "Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes," we have proven expertise and infrastructure and access to a high-enrolling maternal-infant clinical cohort to study how maternal antibiotics alter breast milk composition and impact infant outcomes in clinically meaningful ways.

In the basic science project, "The Impact of Ampicillin and Breast Milk Oligosaccharides on the Infant Microbiome and Immune Functions," we leverage extensive experience in mouse models of neonatal host-pathogen interactions to probe the functional effects of ampicillin and MMOS on infant immune function, including a novel cross-fostering strategy with wild-type and MMO-deficient mothers.

In our data science project, "Impact of Maternal Antibiotics on the Breastfeeding Infant Microbiome and Metabolome," we deploy advanced MS technology, non-invasive sampling, and innovative molecular networking analytics in a cutting-edge study of the impact of breast milk antibiotic exposure on the infant microbiome, metabolome, and hepatic CYP enzymes.

The MAC provides milk collection protocols and kits, near-infrared spectroscopy and HPLC, HMO/MMO and nutritional composition analysis, and new assay validation expanding our MPRINT CET analytical capabilities, while the PACC develops and validates novel quantitative assays and physiologic and semi-physiologic models to describe and predict maternal and infant antibiotic PK during breastfeeding.

Our administrative core oversees the integration and performance of our research projects/cores and their milestones, connecting them to the national MPRINT CET hub and unique training/pilot projects.

San Diego University Of California

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

La Jolla, California 920930831 United States

Single Zip Code

Maternal and Pediatrics Precision in Therapeutics Hub (MPRINT) (P50 Clinical Trial Optional) (RFA-HD-21-026)

COVID-19 $3,069,641 (21%) percent of this Project Grant was funded by COVID-19 emergency acts including the American Rescue Plan Act of 2021.
Amendment Since initial award the total obligations have increased 1070% from $1,250,000 to $14,622,009.