Recent understanding of human milk oligosaccharides in establishing infant gut microbiome and roles in immune system

2021 ◽  
pp. 110884
Author(s):  
Ravindra Pal Singh ◽  
Jayashree Niharika ◽  
Kanthi Kiran Kondepudi ◽  
Mahendra Bishnoi ◽  
Jagan Mohan Rao Tingirikari
Author(s):  
Sarah E Maessen ◽  
José G B Derraik ◽  
Aristea Binia ◽  
Wayne S Cutfield

ABSTRACT Obesity begins early but has lifelong consequences for health and well-being. Breastfeeding is thought to be preventive against obesity, but the extent and cause of this association are not well understood. Human milk oligosaccharides (HMOs) are abundant in human milk and not present in commercially available infant formula. These complex sugars are thought to contribute to the development of the infant gut microbiome and immune system. Recently, they have been investigated as a potential link between breastfeeding and lower obesity risk. So far, only a few human studies have examined HMO composition of human milk in association with the infant′s concurrent anthropometry or subsequent growth in infancy, with conflicting results. However, HMOs have been shown to modulate the gut microbiome profile by selectively promoting the growth of specific bacteria, such as bifidobacteria. Moreover, there are differences in the gut microbiome of lean and obese humans, and there is some evidence that the early composition of the gut microbiome can predict later obesity. Although it seems that HMOs might have a role in infant growth and adiposity, there is not enough consistent evidence to understand their potential role in obesity prevention. More data, particularly from large or longitudinal studies, are needed to clarify the functions of HMOs and other breast-milk components in determining long-term health.


2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Sasirekha Ramani ◽  
Christopher J. Stewart ◽  
Daniel R. Laucirica ◽  
Nadim J. Ajami ◽  
Bianca Robertson ◽  
...  

mSystems ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Yaqiang Bai ◽  
Jia Tao ◽  
Jiaorui Zhou ◽  
Qingjie Fan ◽  
Man Liu ◽  
...  

ABSTRACT The milk glycobiome has a significant impact on the gut microbiota of infants, which plays a pivotal role in health and development. Fucosylated human milk oligosaccharides (HMOs) and N-glycans on milk proteins are beneficial for the development of healthy gut microbiota, and the fucosylation levels of these glycans can be affected by the maternal fucosyltransferase 2 gene (FUT2). Here, we present results of longitudinal research on paired milk and stool samples from 56 Chinese mothers (CMs) and their breast-fed children. Changes of HMOs and fucosylated N-glycans in milk of CMs at different lactation stages were detected, which allowed characterization of the major differences in milk glycans and consequential effects on the gut microbiome of infants according to maternal FUT2 status. Significant differences in the abundance of total and fucosylated HMOs between secretor and nonsecretor CMs were noted, especially during early lactation. Despite a tendency toward decreasing milk protein concentrations, the fucosylation levels of milk N-glycans increased during late lactation. The changes in the levels of fucosylated HMOs and milk N-glycans were highly correlated with the growth of Bifidobacterium spp. and Lactobacillus spp. in the gut of infants during early and later lactation, respectively. Enriched expression of genes encoding glycoside hydrolases, glycosyl transferases, ATP-binding cassette (ABC) transporters, and permeases in infants fed by secretor CMs contributed to the promotion of these bacteria in infants. Our data highlight the important role of fucosylated milk glycans in shaping the gut microbiome of infants and provide a solid foundation for development of “personalized” nutrition for Chinese infants. IMPORTANCE Human milk glycans provide a broad range of carbon sources for gut microbes in infants. Levels of protein glycosylation in human milk vary during lactation and may also be affected by the stages of gestation and lactation and by the secretor status of the mother. This was the first study to evaluate systematically dynamic changes in human milk oligosaccharides and fucosylated N-glycans in the milk of Chinese mothers with different secretor statuses during 6 months of lactation. Given the unique single nucleotide polymorphism site (rs1047781, A385T) on the fucosyltransferase 2 gene among Chinese populations, our report provides a specific insight into the milk glycobiome of Chinese mothers, which may exert effects on the gut microbiota of infants that differ from findings from other study cohorts.


The Analyst ◽  
2018 ◽  
Vol 143 (2) ◽  
pp. 536-548 ◽  
Author(s):  
Amr El-Hawiet ◽  
Yajie Chen ◽  
Km Shams-Ud-Doha ◽  
Elena N. Kitova ◽  
Pavel I. Kitov ◽  
...  

Human milk oligosaccharides (HMOs) afford many health benefits to breast-fed infants, such as protection against infection and regulation of the immune system, through the formation of non-covalent interactions with protein receptors.


2021 ◽  
Vol 12 ◽  
Author(s):  
Anaïs Rousseaux ◽  
Carole Brosseau ◽  
Sophie Le Gall ◽  
Hugues Piloquet ◽  
Sébastien Barbarot ◽  
...  

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1038 ◽  
Author(s):  
Julio Plaza-Díaz ◽  
Luis Fontana ◽  
Angel Gil

Maternal milk contains compounds that may affect newborn immunity. Among these are a group of oligosaccharides that are synthesized in the mammary gland from lactose; these oligosaccharides have been termed human milk oligosaccharides (HMOs). The amount of HMOs present in human milk is greater than the amount of protein. In fact, HMOs are the third-most abundant solid component in maternal milk after lactose and lipids, and are thus considered to be key components. The importance of HMOs may be explained by their inhibitory effects on the adhesion of microorganisms to the intestinal mucosa, the growth of pathogens through the production of bacteriocins and organic acids, and the expression of genes that are involved in inflammation. This review begins with short descriptions of the basic structures of HMOs and the gut immune system, continues with the beneficial effects of HMOs shown in cell and animal studies, and it ends with the observational and randomized controlled trials carried out in humans to date, with particular emphasis on their effect on immune system development. HMOs seem to protect breastfed infants against microbial infections. The protective effect has been found to be exerted through cell signaling and cell-to-cell recognition events, enrichment of the protective gut microbiota, the modulation of microbial adhesion, and the invasion of the infant intestinal mucosa. In addition, infants fed formula supplemented with selected HMOs exhibit a pattern of inflammatory cytokines closer to that of exclusively breastfed infants. Unfortunately, the positive effects found in preclinical studies have not been substantiated in the few randomized, double-blinded, multicenter, controlled trials that are available, perhaps partly because these studies focus on aspects other than the immune response (e.g., growth, tolerance, and stool microbiota).


Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3198
Author(s):  
Yingying He ◽  
Zhicheng He ◽  
Serena Leone ◽  
Shubai Liu

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.


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