Abstract

Exosomes are abundance in human body fluids like urine, milk and blood. They act a critical role in extracellular and intracellular communication, intracellular trafficking and physiological regulation. Multiple immune-modulatory components, such as proteins, RNAs and carbohydrates (glycoproteins), have been found in human milk exosomes, which play immune-regulatory functions. However, little is known about oligosaccharides in milk exosomes, the “free sugars”, which act critical roles in the development of infant’s immature mucosal immune system. In this study, the profile of milk exosomes encapsulated human milk oligosaccharides (HMOs) was calibrated with characteristic oligosaccharides in colostrum and mature milk, respectively. The exosomes containing human milk oligosaccharides were uptaken by macrophages, which were responsible for the establishment of intestinal immunity. Furthermore, mice pretreated with exosome encapsulated HMOs were protected from AIEC infection and had significantly less LPS-induced inflammation and intestinal damage. Exosome encapsulated milk oligosaccharides are regarded to provide a natural manner for milk oligosaccharides to accomplish their critical functions in modifying newborn innate immunity. The understanding of the interaction between a mother’s breastfeeding and the development of an infant’s mucosal immune system would be advantageous. The transport of milk oligosaccharides to its target via exosome-like particles appears to be promising.

Highlights

  • IntroductionMother’s milk, as the natural food for infants, contains quantitative and proportional nutrients that promote brain, intestinal, and immune develop rapidly in neonates [1]

  • Mother’s milk, as the natural food for infants, contains quantitative and proportional nutrients that promote brain, intestinal, and immune develop rapidly in neonates [1].Human milk, which contains thousands of indigestible bioactive molecules, has recently been shown to modulate neonate’s intestinal mucosal immunity, protect infants from infection and inflammation damage, and contribute to healthy microbial colonization of the neonatal intestine and promote organs development [2,3]

  • The arm is to test the hypothesis that exosomes are the natural manner for Human milk oligosaccharides (HMOs) to get into immune cells and regulate infant’s mucosal immunity development

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Summary

Introduction

Mother’s milk, as the natural food for infants, contains quantitative and proportional nutrients that promote brain, intestinal, and immune develop rapidly in neonates [1]. Human milk, which contains thousands of indigestible bioactive molecules (protein, microRNA, oligosaccharides), has recently been shown to modulate neonate’s intestinal mucosal immunity, protect infants from infection and inflammation damage, and contribute to healthy microbial colonization of the neonatal intestine and promote organs development [2,3]. There are three major proposed manners and mechanisms for breastfeeding mother’s milk to protect their children that have been postulated, including inhibiting pathogen binding, acting as natural prebiotics, and modulating the development and differentiation of mucosal immune system [1,2,4]. The distribution of milk oligosaccharides that are majority active component in the milk exosomes is poorly understood

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