Evolutionary and Sociocultural Aspects of Human Milk Composition

Study Overview
=================
Brief Summary
-----------------
It is well-known that breastfeeding protects infants from illness, especially in the poorest regions of the world. The full nature of this protective effect, however, is less well understood. A major barrier to understanding is the fact that almost nothing is known about the factors that influence the considerable variation in milk composition around the globe, or about the effects of this variation on infant health. This INSPIRE project represents the first comprehensive investigation of the global differences in human milk composition along with the various microbial, evolutionary, environmental, and sociocultural factors that might influence both milk composition and infant health. An international, interdisciplinary collaboration of physiologists, nutritional scientists, anthropologists, microbiologists, and mathematicians will collect biological data from breastfeeding women and their infants, in concert with extensive anthropologic and ecological data, in both developed (US, Spain, Sweden) and developing countries (Central African Republic, Gambia, Ghana, Peru, and Kenya). To test the possibility of a correlation between milk oligosaccharide composition, milk microbiota, and the gastrointestinal microbiome of infants, milk samples and infant fecal samples will be analyzed using state-of-the-art biochemical and genomic techniques. This study will allow important cross-cultural comparisons of milk composition and infant feeding practices; it also will utilize sophisticated computational methods to integrate the extensive, diverse body of combined biological and anthropological data to elucidate the relationships among sociocultural factors, evolutionary history, environmental exposures, microbial constituents and milk composition. The researchers predict that what is considered normal milk composition in one population may not support optimal health in another. This information is crucial to the humanitarian quest to understand how infant nutrition and overall health can be improved around the world. In addition, this project will provide extensive research training opportunities for undergraduate, graduate and postdoctoral scientists.

Conditions
-----------------
Breast Milk Collection

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Breastfeeding or pumping at least 5 times daily (to assure adequate milk production) Self-reported healthy women and infants ≥ 18 yr of age (maternal) 1-3 mo postpartum Exclusion Criteria Current indication of breast infection (e.g., breast pain, discomfort, lumps, mastitis with fever, red streaks, or hard red portions of the breast) Breast pain that the woman does not consider normal for lactation/breastfeeding Any antibiotics to mother or infant in the previous month (30 days) Infant has had signs/symptoms of acute illness in the previous 7 days including the following: fever, diarrhea (≥ 3 excessively loose stools in a day), vomiting not associated with feeding, severe cough, rapid breathing

Ages Eligible for Study
-----------------
Minimum Age: 1 Month

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| US-Washington, Idaho<br>healthy breastfeeding women and their infants | |
| US-California<br>healthy breastfeeding women and their infants | |
| Sweden<br>healthy breastfeeding women and their infants | |
| Spain<br>healthy breastfeeding women and their infants | |
| Peru<br>healthy breastfeeding women and their infants | |
| Kenya<br>healthy breastfeeding women and their infants | |
| Ethiopia-rural<br>healthy breastfeeding women and their infants | |
| Ethiopia-urban<br>healthy breastfeeding women and their infants | |
| The Gambia-rural<br>healthy breastfeeding women and their infants | |
| The Gambia-urban<br>healthy breastfeeding women and their infants | |
| Ghana<br>healthy breastfeeding women and their infants | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial community structure of milk | Sequencing of microbial 16S gene via MiSeq; data will be analyzed as relative abundances of bacteria from phylum to genus; how milk microbial profiles are related to milk oligosaccharide and infant fecal microbiomes will be explores using multivariate ecological analyses. | 1-3 months postpartum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sociocultural data of women, including dietary intake patterns and microbial exposures | Collected via surveys; multivariate analysis will be conducted to relate these factors to variation in primary outcomes - particularly microbial community structure of milk. | 1-3 months postpartum | 
| Microbial community structure of infant feces | Sequencing of microbial 16S gene via MiSeq; data will be analyzed as relative abundances of bacteria from phylum to genus; relationships with milk microbiome and oligosaccharide profiles will be explored using multivariate ecological analyses. | 1-3 months of life | 
| Oligosaccharide profiles of milk | Total and individual oligosaccharide concentrations will be determined; how oligosaccharide profiles are related to milk and infant microbiomes will be explores using multivariate ecological analyses. | 1-3 months postpartum |