Association Between Human Milk Oligosaccharides and Early Adiposity Rebound in Children: A Case–Control Study of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

Background: Adiposity rebound (AR) is the point when the BMI begins to rise again during early childhood. Early AR (before age 5) is associated with higher risk of lifelong obesity and metabolic disorders and may be influenced by breastfeeding. Although human milk oligosaccharides (HMOs) in breast milk are crucial for child growth, their association with AR status has not been studied. Objectives: This study aimed to explore the association between breast milk HMOs and AR status in children. Methods: In this case–control study, we included 184 mother–child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) Cohort Study (93 AR cases, 91 controls). Breast milk was collected 1 mo postpartum, and the concentration of 15 HMO molecules and α-diversity index (Inverse Simpson index) were quantified. Wilcoxon rank-sum test and partial least squares-discriminant analysis identified candidate HMOs, and multivariable logistic regression analysis evaluated associations between candidate HMOs and AR status. Analyses were stratified by maternal secretor status (secretor or nonsecretor). Results: In secretor mothers, multivariable logistic regression showed that the inverse Simpson index [odds ratio (OR): 0.54; 95% CI: 0.36, 0.82), the sum of sialic acid–bound HMOs (OR: 0.61; 95% CI: 0.41, 0.91), and 3'-sialyllactose (OR: 0.67; 95% CI: 0.46, 0.98) were inversely associated with early AR in the fully adjusted model. A trend of interaction between sialyl-lacto-N-tetraose-a (LSTa) and maternal secretor status regarding AR was observed in the fully adjusted model (P-interaction = 0.051). Conclusions: α-Diversity, sialic acid–bound HMOs, and 3'-sialyllactose may involved in inhibiting AR in children of secretor mothers, and a trend of interactive effect between LSTa and maternal secretor status regarding AR is indicated. These findings offer novel perspectives on the associations between breastfeeding and a childhood adiposity as well as potential metabolic disorders later in life. This trial is registered at https://www.umin.ac.jp/ as UMIN000047160.