Editor’s Choice

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.

Section: Discussionmentioning

confidence: 99%

“…[5] Exosomes are pesent in many body fluids, including human milk. [6] Human milk-derived exosomes contain important biological molecules that play crucial functions in intercellular communication. Recently, we reported that preterm human milk derived exosomes significantly reduced the severity of NEC in vivo.…”

Section: Doi: 101002/mnfr202000845mentioning

confidence: 99%

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

Chen

Qian

et al. 2021

“…Colin et al. reported that human breast milk‐derived exosomes can protect intestinal epithelial cells (IECs) from oxidative stress induced cell death . Alison et al.…”

Section: Discussionmentioning

confidence: 99%

“…Exosomes are small, endocytic vesicular bodies (30-200 nm) present in various body fluids and are especially highly present in breast milk. [5,6] Milk-derived exosomes encapsulate various types of cargos, such as proteins, mRNAs, and microRNAs (miR-NAs), and protect them from enzymatic and non-enzymatic degradation. [7] Therefore, milk exosomes bear important biological functions in mediating cell-to-cell communication among distant cells.…”

Section: Introductionmentioning

confidence: 99%

Identification and Peptidomic Profiling of Exosomes in Preterm Human Milk: Insights Into Necrotizing Enterocolitis Prevention

Xingyun

Yan

Zhang

et al. 2019

Scope Human breast milk has been shown to prevent necrotizing enterocolitis (NEC). Although exosomes have been identified in breast milk, their function and components have not been fully addressed. This study is conducted to elucidate the differences in peptidomic complexities between preterm and term milk exosomes. Methods and results Breast milk samples are collected from healthy lactating mothers who have delivered term and preterm infants. Exosomes are separated and quantified. The protective effects of purified exosomes against NEC are investigated both in vitro and in vivo. The peptidomic complexities in term and preterm milk exosomes are analyzed by iTRAQ LC‐MS/MS to screen differentially expressed exosomal peptides. Preterm milk exosomes administration significantly enhances proliferation and migration of intestinal epithelial cells compared with term milk exosomes. A total of 70 peptides are found to be significantly modulated in preterm milk samples compared to term milk samples. Of these, 47 peptides are upregulated, and 23 peptides are downregulated. Bioinformatics analysis suggests several potential regulatory roles of the altered peptides in intestinal epithelial cell function. Conclusion These results reveal the differences for the first time in peptidomic complexities between preterm and term milk exosomes. Milk exosome administration might be a promising prevention for NEC.

“…Studies have reported that M-sEVs can attenuate the severity of colitis induced by DSS, [2,38,39] and had pro-proliferative and antiapoptotic effects in both rat (IEC-6) and human (FHS74) intestinal cell culture models, [16,18] as well as abrogated H 2 O 2induced increase in cell death. [40] However, few studies have ex-plored the role of M-sEVs on repairing damaged intestinal epithelia. We investigated the effect of M-sEVs on repairing intestinal damage using colitis models in mice and IOs.…”

Section: Discussionmentioning

confidence: 99%

Milk‐Derived Small Extracellular Vesicles Promote Recovery of Intestinal Damage by Accelerating Intestinal Stem Cell‐Mediated Epithelial Regeneration

Lin

Yao

Huang

et al. 2022

Scope: Milk-derived small extracellular vesicles (M-sEVs) are critical bioactive components in milk. They are considered to be regulators in milk that may have promising applications. Understanding their biological effects would be important in nutrition. Intestinal organoids and mice are used to explore the effects of M-sEVs on intestinal regeneration. Methods and results: M-sEVs could be absorbed by intestinal epithelia and upregulate expression of the microRNAs (miRNAs) expressed in milk: miR-148a, miR-22, miR-30, and miR-29a. Interestingly, M-sEVs promote proliferation of intestinal epithelia and repairs the epithelial damage that is caused by tumor necrosis factor-𝜶 in intestinal organoids. M-sEVs ameliorate intestinal mucosa damage in mice caused by treatment with dextran sulfate sodium, as well as increasing expression of the intestinal stem cells (ISC) markers leucine-rich repeat containing G-protein-coupled receptor 5 (Lgr5), olfactomedin 4 (Olfm4), and Achaete-Scute Family BHLH Transcription Factor 2 (Ascl2) and stimulating intestinal epithelial proliferation to repair epithelial damage. Furthermore, miR-29 is more abundant in M-sEVs-treated mice, and miR-29 could upregulate expression of ISC marker genes and accelerates intestinal regeneration to recover damaged intestinal epithelia. Conclusions: We reveal that M-sEVs and miR-29 can accelerate intestinal stem cell-mediated epithelial regeneration and repair epithelial damage.