An exploration of the breast milk nutriome, exposome and microbiome and their links to early growth in preterm infants

Breastfeeding promotes improved growth and development in preterm infants, yet the mechanisms underlying these benefits remain unclear. This study explored the interplay of breast-milk nutritional, microbiological, and environmental chemical exposure on early preterm infant growth. In the prospective LACTACOL-cohort, growth was assessed in 137 exclusively breastfed preterm infants (including 40 twins) using Z-scores of discharge weight and fat-free mass (FFM, by air-displacement plethysmography). Breast-milk samples were analyzed for their nutriome (targeted and untargeted metabolomic and lipidomic profiling), exposome (targeting persistent organic pollutants, POPs), and microbiome (16s rDNA-sequencing). Correlation analysis and sequential random forest modeling were applied to integrate multi-omics datasets and identify determinants of discharge weight Z-score (36 observations) and FFM (21 observations). The nutriome emerged as the primary contributor to the postnatal growth in preterm infants. Choline-containing lipids (sphingolipids, phosphatidylcholines and their plasmalogen forms), positively contributed to weight Z-score. Sphingomyelin enriched in nervonic acid supported positively FFM Z-score, whereas oxylipins had a negative effect. The exposome exhibited complex effects: the dioxin-like compound 1,2,3,7,8-PeCDD negatively impacted weight, while the polychlorinated biphenyl 123 positively influenced both weight and lean mass gains. Brominated flame retardants were associated with a lower FFM Z-score. Although the microbiome showed an overall minor impact, it varied with POPs and postnatal growth terciles, highlighting the co-dependencies between milk components. This integrative hypothesis-generating pilot study provides novel evidence on the richness of breast-milk composition and the interplay of nutriome, exposome, microbiome in breast-milk and their joint influence on postnatal growth in preterm infants. Clinical Trial Registry: LACTACOL, ClinicalTrials.gov ID NCT NCT01493063 https://clinicaltrials.gov/study/NCT01493063.