Human milk oligosaccharides, gut microbiome and obesity in infants

Funder: Gerber Foundation Grant
Funding PeriodL January 2016 for 3 years

This study aims to identify novel factors in human breast milk that affect development of the infant gut bacterial profile (the microbiome), and in turn contribute to infant growth and/or accumulation of excess body fat by 24 months of age. By comparing infants of mothers who were overweight/obese versus normal weight before pregnancy, we will also gain important insights into infant growth and development for infants at higher-risk versus lower-risk of developing obesity in early-life. Our main outcomes are significant because rapid infant growth and excess body fat by 24 months of age are well-established risk factors for future obesity and metabolic complications like type 2 diabetes. We will focus on human milk oligosaccharides (HMOs), complex sugars that are present in high and variable amounts in breast milk and are known to significantly contribute to establishing the infant immune system. Since HMOs cannot be digested and reach the colon intact, another less well studied effect of HMOs is that they can also act as prebiotics, promoting the growth of beneficial microorganisms in the intestine, potentially contributing to development of the infant gut microbiome. The gut microbiome is now known to play an important role in establishing long-term predisposition to a wide variety of diseased states, including obesity. We hypothesize that individual differences in HMOs in breast milk contribute to differences in infant growth rates and/or the development of early-onset obesity through their effects on the developing infant gut microbiome. We have established preliminary evidence in support of this novel theory in a small pilot study that followed infants to 6 months of age. In this new study, we will extend our initial observation to a larger sample of 80 mothers and infants, measure infant body fat out to 24 months of age, and examine whether the effect of HMOs on infant obesity is explained by their effect on the developing infant gut microbiota. In addition, we will examine whether differences in HMOs and/or the developing infant gut microbiota can explain the greater propensity for early onset obesity in infants born to mothers who were overweight/obese before pregnancy, as compared to infants on healthy weight mothers.

We will recruit 80 mother-infant pairs, with an even split of women who were overweight/obese versus normal weight before pregnancy. Mothers and infants will be monitored during the first 24 months of life, with frequent sampling of breast milk as well as infant and maternal stool. Maternal and infant dietary intake will also be determined using 24-hour recalls in mothers and validated maternal questionnaires for infant intake. The main outcome measures will be infant body weight-for-length trajectory during this period, as well as infant body composition (fat and lean mass), measured by dual energy x-ray absorptiometry (DEXA). To achieve our goal of integrating complex metabolic, physiological and nutritional outcomes using the most advanced technology possible, we have assembled a diverse multi-disciplinary research team of internationally recognized leaders in the field. This team has established a unique collaborative working group that provides expertise in infant and child obesity/nutrition and human clinical studies (Michael Goran, USC), human milk oligosaccharides (Lars Bode, UCSD), gut microbiome (Rob Knight, UCSD), and breast milk composition/infant body composition (David Fields, OUHSC).