Bovine milk-derived exosomes attenuate NLRP3 inflammasome and NF-κB signaling in the lung during neonatal necrotizing enterocolitis

Abstract

PurposeNecrotizing enterocolitis (NEC), an in ammatory intestinal disease common in premature infants, has been associated with the development of lung damage. Toll-like receptor 4 has been shown to regulate in ammation in the NEC lungs, however, other important in ammatory mechanisms have not been thoroughly investigated. In addition, we reported that milk-derived exosomes were able to attenuate intestinal injury and in ammation in experimental NEC. This study aims to (i) investigate the role of the NLRP3 in ammasome and NF-κB pathway in regulating lung damage during experimental NEC; and (ii) evaluate the therapeutic potential of bovine milk exosomes in reducing lung in ammation and injury during NEC. Methods NEC was induced by gavage feeding of hyperosmolar formula, hypoxia, and lipopolysaccharide administration in neonatal mice from postnatal days 5-9. Exosomes were obtained by ultracentrifugation of bovine milk and administered during each formula feed. ResultsThe lung of NEC pups showed increased in ammation, tissue damage, NLRP3 in ammasome expression, and NF-κB pathway activation, which were attenuated upon exosome administration. ConclusionOur ndings suggest that the lung undergoes signi cant in ammation and injury following experimental NEC which are attenuated by bovine milk-derived exosomes. This emphasizes the therapeutic potential of exosomes not just on the intestine but also on the lung.

Application of Milk Exosomes for Musculoskeletal Health: Talking Points in Recent Outcomes

“…In the intestine, the preventive effect of milk-derived exosomes against the development of necrotizing enterocolitis, which is characterized by intestinal injury and impaired mucin synthesis, is mediated by the promotion of goblet cell expression/production and ER functioning [80]. Attenuation of inflammasomes in the lungs during neonatal NEC has also been demonstrated by treatment with bovine milk exosomes [81]. The alleviation of cardiac fibrosis and enhancement of cardiac function in rats with cardiac fibrosis by enhanced angiogenesis have also been reported [82].…”

Milk-Derived Extracellular Vesicles: Biomedical Applications, Current Challenges, and Future Perspectives

“…High-throughput analysis can also help in identifying specific markers for different miEVs subpopulations and even distinguishing them from each other. Given that the harsh industrial processing disrupts the concentration, content, and quality of miEVs in IMF, ,, recent studies have proposed the addition of miEVs to IMF as a potential strategy to improve the infant’s health. ,, However, further research is required to determine its safety and efficacy. Moreover, given that milk proteins, such as casein, significantly contribute to cow’s milk allergy in infants, it is crucial to optimize isolation methods to reduce miEVs allergenic potential. While numerous researches have highlighted miEVs as potential therapeutics, these are primarily based on mice models. ,, Although these rodent-based studies offer crucial insights into the therapeutic impacts of miEVs, the findings may not be entirely applicable to humans. This necessitates further research on models that are physiologically closer to humans, such as nonhuman primate .…”

“…While numerous researches have highlighted miEVs as potential therapeutics, these are primarily based on mice models. ,, Although these rodent-based studies offer crucial insights into the therapeutic impacts of miEVs, the findings may not be entirely applicable to humans. This necessitates further research on models that are physiologically closer to humans, such as nonhuman primate .…”

Chromatin as alarmins in necrotizing enterocolitis

“…The miRNA mimic (miR-146a-5p) inhibited NLRP3 inflammasome downstream inflammatory factors in cells and is another possible relevant factor in inflammatory signaling in NEC (41). Moreover, treatment with bovine milkderived exosomes in an animal model of NEC attenuated lung injury by reducing NLRP3 inflammasome activation and NF-kB signaling (84).…”