Breastmilk polyamines modify gut gene expression in children at three months of age

Abstract

Background & aims: Breastmilk is one of the main sources of exogenous polyamines for newborns and contains higher polyamine content than infant formulas. Polyamines are involved in gut maturation and immune system regulation in animals, although the underlying mechanisms are not fully understood. We quantified polyamines in human mature breastmilk and evaluate their effects on intestinal gene expression in babies at three months of age.

Methods: Polyamines were quantified in mature milk of 195 women from the prospective Mediterranean NELA birth cohort (Murcia, Spain) at 3 months postpartum. Maternal dietary intake was assessed by food frequency questionnaires. Intestinal gene expression was analysed in babies receiving breastmilk, with high (>p50, n = 25) or low (<p50, n = 27) polyamine content, at 3 m of age, by microarray using a non-invasive method on gut exfoliated cells.

Results: Spermidine and spermine were the most prevalent polyamines in breastmilk at 3 months postpartum, while levels of putrescine were lower. Maternal dietary intake of polyamines was not associated with polyamine concentration in breastmilk and there were no differences in the polyamine content between allergic and non-allergic mothers. Microarray analyses of exfoliated gut cells revealed that cell localization and immune system were the most significant biological processes affected by high vs low polyamines in breastmilk. There were 15 differentially expressed genes, 3 up-regulated and 12 down-regulated, in high compared to low polyamine groups. Among the up-regulated genes were tumour necrosis factor alpha-induced protein 6 (TNFAIP6) and interleukin 8; while other immune system-related genes, such as integral membrane protein 2C, lymphocyte antigen 6 complex, transmembrane protein 179B were down-regulated.

Conclusions: Mature breastmilk presents spermidine and spermine as the most prevalent polyamines. Babies receiving milk with higher polyamine levels showed differences in the expression of genes associated with cell localization and immune system processes.

Keywords: Breastmilk; Exfoliome; Gene expression; Intestine; Polyamines; Transcriptome.