A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury

Gao, Runnan; Zhang, Rong; Tian, Qing; Peng, Xueni; He, Weijing; Zheng, Shan; Cao, Yun; Pierro, Agostino; Shen, Chun

doi:10.1007/s00383-019-04562-6

Cited by 61 publications

(62 citation statements)

References 20 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: 82%

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: 82%

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

et al. 2020

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“…Meta-analyses suggest a benefit in feeding mother's own milk (29) and pasteurized donor human milk (30) in the prevention of BPD. In organoids derived from the terminal ileum of mouse pups, human milk exosomes have been shown to attenuate LPS induced activation of TLR4 (31). Human milk oligosaccharides interact with TLR4 on the surface of dendritic cells inducing immune tolerance through increased generation of regulatory T cells and attenuation of LPS-induced expression of IL6 and TNFα (32).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

et al. 2020

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Background: In extremely premature infants, postnatal growth restriction (PNGR) is common and increases the risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Mechanisms by which poor nutrition impacts lung development are unknown, but alterations in the gut microbiota appear to play a role. In a rodent model, PNGR plus hyperoxia causes BPD and PH and increases intestinal Enterobacteriaceae, Gram-negative organisms that stimulate Toll-like receptor 4 (TLR4). We hypothesized that intestinal dysbiosis activates intestinal TLR4 triggering systemic inflammation which impacts lung development. Methods: Rat pups were assigned to litters of 17 (PNGR) or 10 (normal growth) at birth and exposed to room air or 75% oxygen for 14 days. Half of the pups were treated with the TLR4 inhibitor TAK-242 from birth or beginning at day 3. After 14 days, pulmonary arterial pressure was evaluated by echocardiography and hearts were examined for right ventricular hypertrophy (RVH). Lungs and serum samples were analyzed by western blotting and immunohistochemistry. Results: Postnatal growth restriction + hyperoxia increased pulmonary arterial pressure and RVH with trends toward increased plasma IL1β and decreased IκBα, the inhibitor of NFκB, in lung tissue. Treatment with the TLR4 inhibitor attenuated PH and inflammation. Conclusion: Postnatal growth restriction induces an increase in intestinal Enterobacteriaceae leading to PH. Activation of the TLR4 pathway is a promising mechanism by which intestinal dysbiosis impacts the developing lung.

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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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A comparison of exosomes derived from different periods breast milk on protecting against intestinal organoid injury

Cited by 61 publications

References 20 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

Intestinal Dysbiosis and the Developing Lung: The Role of Toll-Like Receptor 4 in the Gut-Lung Axis

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

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