Milk and infant plasma hormone concentrations predict sweet and fat taste acceptance and later food intake

Early-life exposure to metabolic hormones may influence the development of taste acceptance and subsequent intake of hyperpalatable foods (HPF) in infants, but evidence integrating hormonal, behavioral, and dietary data in humans is limited. Therefore, our objective was to determine whether concentrations of insulin, leptin, cortisol, and liver-expressed antimicrobial peptide 2 (LEAP2) in human milk and infant plasma at 6 months predict infant sweet and fat taste acceptance and HPF intake later in infancy. In this prospective cohort study, human milk and infant plasma were collected at 6 months and analysed for insulin, leptin, cortisol, and LEAP2. At 18 months, sweet and fat taste acceptance were assessed using ingestion ratio (IR; motivational drive) and liking ratio (LR; hedonic response). HPF intake was quantified from standardized 24-h dietary recalls. Associations were evaluated using multivariable linear regression. Eighty two mother-infant pairs were enrolled, of which 28 completed follow-up and were included in the final analysis. Milk LEAP2 was positively associated with fat IR (p = .037). Milk insulin was inversely associated with sweet IR (p = .003) and LR (p = .020), while milk leptin was positively associated with sweet IR (p = .013) and LR (p = .018) and inversely associated with HPF intake consumption (p = .001). Milk cortisol was positively associated with fat (p = .043) and sweet IR (p = .014). In contrast, infant plasma LEAP2 was inversely associated with fat IR (p = .018) and HPF intake (p = .002) but positively associated with sweet IR (p = .005) and LR (p = .023). Infant plasma cortisol was directly associated with HPF intake (p = .006) and inversely associated with sweet and IR (p = .004) and fat LR (p = .009). Milk-derived and endogenous metabolic hormones were differentially associated with taste acceptance and HPF intake, identifying specific hormonal pathways that may shape early feeding behavior and later food intake. Clinical Trial Registry: This study was registered at clinicaltrials.gov as NCT05798676. https://clinicaltrials.gov/study/NCT05798676.