Omics approaches highlight milk molecules impacting offspring early gut maturation
Résumé
OBJECTIVES: Milk composition is complex and includes numerous components essential for offspring growth and development. In addition to the high abundance of miR-30b microRNA, milk produced by the transgenic mouse model of miR-30b-mammary deregulation displays a significantly altered fatty acid profile. Moreover, wild-type adopted pups fed with this milk present an early growth defect. This study aimed to investigate the consequences of miR-30b milk feeding on neonatal gut development, a prime target of suckled milk, along with comprehensive milk phenotyping.
METHODS: The duodenum of wild-type pups fed miR-30b milk was extensively characterized at postnatal day-5, day-6 and day-15 using histological, transcriptomic, proteomic, and intestinal permeability analyses, and compared to pups fed wild-type milk. Milk of miR-30b foster dams collected at mid-lactation was extensively analyzed using proteomic, metabolomic, lipidomic approaches and hormonal immunoassays.
RESULTS: At postnatal day-5, pups fed miR-30b milk showed maturation of their gut tissue (increase expression of claudins and changes in eight duodenal protein), with an earlier reduction in paracellular and transcellular permeability. Compared to wild-type milk, miR-30b milk displayed an increase in total lipid, ceramide and sphingomyelin levels, the over-expression of nine proteins involved in the gut barrier, and higher insulin and leptin levels.
CONCLUSIONS: Integrative systems biology with omics approaches highlight significant changes of bioactive components in miR-30b milk associated with neonatal gut integrity and maturation, that could be involved in the earlier intestinal closure phenotype of the pups, which is associated with a lower growth rate.