Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis

Abstract

Scope: Human milk can prevent the development of necrotizing enterocolitis (NEC). Human milk is rich in cargo-carrying exosomes that participate in intercellular communication. This study investigated the effects of term and preterm human milk-derived exosomes, and elucidated their lipid expression profiles. Methods and Results: Milk from healthy mothers is collected who have delivered full-term or preterm infants, and exosomes are isolated and quantified. Administration of term and preterm milk exosomes significantly enhances epithelial proliferation and migration in vitro, and ameliorates the severity of NEC in vivo. A total of 395 lipids are identified in term and preterm human milk-derived exosomes. Bioinformatics analysis and western blotting reveal that top 50 lipids regulate intestinal epithelial cell function via the Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway. Conclusion: This study reveals for the first time the lipidomic complexities in exosomes derived from preterm and term milk. The results provide novel mechanistic insight on how human milk prevents the development of NEC.

Beneficial Effects of Bovine Milk Exosomes in Metabolic Interorgan Cross-Talk

“…These effects were independent of the delivery status [ 126 ]. Other authors have reported similar effects of HME on the incidence and severity of NEC in rat models [ 70 , 127 ]. In particular, Chen et al observed that HME isolated from women who gave birth to term or preterm newborns exerted a protective effect on NEC by decreasing the severity of the injury and stimulating the proliferation and migration of intestinal epithelial cells independently of the delivery status [ 70 ].…”

“…Other authors have reported similar effects of HME on the incidence and severity of NEC in rat models [ 70 , 127 ]. In particular, Chen et al observed that HME isolated from women who gave birth to term or preterm newborns exerted a protective effect on NEC by decreasing the severity of the injury and stimulating the proliferation and migration of intestinal epithelial cells independently of the delivery status [ 70 ]. The authors further analyzed the lipidomic profile of HME, finding that term and preterm milk exosomes displayed almost identical lipid compositions.…”

“…Contrary to proteins, the lipid composition of exosomes remains largely unexplored. Lipidomic analyses of milk-derived exosomes have revealed that phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), and sphingomyelin (SM) are among the most enriched lipids found in these vesicles [ 25 , 70 , 71 ]. PC has been proposed to ameliorate inflammation via the gut–brain axis in vivo [ 72 ].…”

“…Evidence from human trials attributes a positive effect to MFGM lipids in growth, intestinal health, and infant neurodevelopment [ 75 ]. These effects are usually attributed to polar lipids, which are also abundantly expressed in milk exosomes [ 70 ]. However, research on the beneficial effects of the lipidic fraction of milk exosomes is lacking and constitutes an interesting avenue to explore [ 75 ].…”

“…Furthermore, exosomes have been shown to confer protection against the adverse conditions present in the digestive tract, which suggests that the oral intake of these compounds facilitates the availability of their cargos [ 86 , 87 , 88 ]. Besides protecting their cargos, glycoproteins displayed in milk exosomes facilitate their recognition and uptake by the target cell receptors [ 70 , 89 ].…”