Human breast milk exosomes attenuate intestinal damage

Miyake, Hideaki; Lee, Carol; Chusilp, Sinobol; Bhalla, Manvi; Li, Bo; Pitino, Michael A.; Seo, Shogo; O'Connor, Deborah L; Pierro, Agostino

doi:10.1007/s00383-019-04599-7

Cited by 105 publications

(103 citation statements)

References 31 publications

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“…Breast milk provides complex lipids through the delivery of MFGMs and exosomes. Published data support the role of extracellular vesicles on intestinal development and protection from intestinal injury such as NEC [112][113][114]. When evaluated in totality versus in individual components, human milk-derived exosomes attenuate oxidative stress-induced cell death in intestinal epithelial cells [115] and enhance proliferation and migration of intestinal epithelial cells in preterm infants compared to those with full term birth [116].…”

Section: Complex Lipidsmentioning

confidence: 83%

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

et al. 2020

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Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.

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Section: Complex Lipidsmentioning

confidence: 83%

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

et al. 2020

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“…Whether nonabsorbed exosomes also act from the luminal side is not elucidated. Recent evidence indicates that milk exosomes play a critical role for intestinal maturation and function in humans and rodent models [22][23][24][25][26][27][28]. It has been demonstrated in murine models that human, bovine, and porcine milk exosomes support intestinal cell growth [22][23][24], attenuate LPS-induced apoptosis [25], prevent intestinal endothelial cell damage [26,27], enhance goblet cell numbers and mucin production [28], modify bacterial growth, and promote intestinal microbiota [29,30].…”

Section: Introductionmentioning

confidence: 99%

“…Recent evidence indicates that milk exosomes play a critical role for intestinal maturation and function in humans and rodent models [22][23][24][25][26][27][28]. It has been demonstrated in murine models that human, bovine, and porcine milk exosomes support intestinal cell growth [22][23][24], attenuate LPS-induced apoptosis [25], prevent intestinal endothelial cell damage [26,27], enhance goblet cell numbers and mucin production [28], modify bacterial growth, and promote intestinal microbiota [29,30]. Accumulating evidence indicates that milk exosomes exert barrier-protective and anti-inflammatory effects in rodent models of necrotizing enterocolitis (NEC) and NEC in human infants [25][26][27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Stremmel¹,

Weiskirchen

Melnik

2020

Inflamm Intest Dis

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Background: Milk is rich in nutrients and anabolic mediators rendering it essential for postnatal growth and metabolic programming. However, in adults, excessive consumption of milk is controversial as civilization disorders such as diabetes or prostate cancer may be promoted. A cytoprotective effect of milk could be utilized in inflammatory conditions, that is, chronic colitis. Objective: To evaluate the effect of bovine milk exosomes on intestinal inflammation in a genetic mouse model of ulcerative colitis. Methods: Intestinal-specific kindlin 2 knockout (KO) mice were exposed for 4 days to tamoxifen for induction of an ulcerative colitis phenotype. At the same time 4 other kindlin 2 KO mice were exposed to 33 μg/g cow milk derived exosomes in PBS by oral gavage. Both groups were compared to untreated wild-type controls. Results: Milk exosomes prevented the appearance of a severe ulcerative phenotype. The macroscopic colitis score dropped from a mean of 3.33 in untreated mice to 0.75 index points (p < 0.01) in exosome-treated mice, which included significant improvement of the subscores of stool improvement and colon weight and length. Treated mice featured a noninflamed appearance of the intestinal mucosa. Key Message: Milk exosomes have cytoprotective/anti-inflammatory activity in a genetic mouse model of ulcerative colitis. The mechanisms behind this need to be elucidated. This pilot study needs verification before a therapeutic strategy is developed.

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“…Consistently, Martin et al have also reported that human milk-derived exosomes protect intestinal epithelial cells from cell death upon exposure to oxidative stress [ 63 ]. Furthermore, a neonatal mouse intestinal organoid model and experimental NEC in C57BL/6 mouse pups supported the protective activities of HBM exosomes by decreasing inflammation and intestinal damage [ 64 ]. A reduction in intestinal damage has also been observed by exosomes derived from pasteurized breast milk and raw breast milk, indicating that milk exosomes are resistant to the pasteurization process.…”

Section: Breast Milk-derived Exosomesmentioning

confidence: 99%

More than Nutrition: Therapeutic Potential of Breast Milk-Derived Exosomes in Cancer

Kim

Jeong

et al. 2020

IJMS

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Human breast milk (HBM) is an irreplaceable source of nutrition for early infant growth and development. Breast-fed children are known to have a low prevalence and reduced risk of various diseases, such as necrotizing enterocolitis, gastroenteritis, acute lymphocytic leukemia, and acute myeloid leukemia. In recent years, HBM has been found to contain a microbiome, extracellular vesicles or exosomes, and microRNAs, as well as nutritional components and non-nutritional proteins, including immunoregulatory proteins, hormones, and growth factors. Especially, the milk-derived exosomes exert various physiological and therapeutic function in cell proliferation, inflammation, immunomodulation, and cancer, which are mainly attributed to their cargo molecules such as proteins and microRNAs. The exosomal miRNAs are protected from enzymatic digestion and acidic conditions, and play a critical role in immune regulation and cancer. In addition, the milk-derived exosomes are developed as drug carriers for delivering small molecules and siRNA to tumor sites. In this review, we examined the various components of HBM and their therapeutic potential, in particular of exosomes and microRNAs, towards cancer.

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Human breast milk exosomes attenuate intestinal damage

Cited by 105 publications

References 31 publications

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Breast Milk Lipids and Fatty Acids in Regulating Neonatal Intestinal Development and Protecting against Intestinal Injury

Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

More than Nutrition: Therapeutic Potential of Breast Milk-Derived Exosomes in Cancer

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