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Immunomodulation by Human Milk Oligosaccharides: The Potential Role in Prevention of Allergic Diseases.
Zuurveld, M, van Witzenburg, NP, Garssen, J, Folkerts, G, Stahl, B, Van't Land, B, Willemsen, LEM
Frontiers in immunology. 2020;:801
Abstract
The prevalence and incidence of allergic diseases is rising and these diseases have become the most common chronic diseases during childhood in Westernized countries. Early life forms a critical window predisposing for health or disease. Therefore, this can also be a window of opportunity for allergy prevention. Postnatally the gut needs to mature, and the microbiome is built which further drives the training of infant's immune system. Immunomodulatory components in breastmilk protect the infant in this crucial period by; providing nutrients that contain substrates for the microbiome, supporting intestinal barrier function, protecting against pathogenic infections, enhancing immune development and facilitating immune tolerance. The presence of a diverse human milk oligosaccharide (HMOS) mixture, containing several types of functional groups, points to engagement in several mechanisms related to immune and microbiome maturation in the infant's gastrointestinal tract. In recent years, several pathways impacted by HMOS have been elucidated, including their capacity to; fortify the microbiome composition, enhance production of short chain fatty acids, bind directly to pathogens and interact directly with the intestinal epithelium and immune cells. The exact mechanisms underlying the immune protective effects have not been fully elucidated yet. We hypothesize that HMOS may be involved in and can be utilized to provide protection from developing allergic diseases at a young age. In this review, we highlight several pathways involved in the immunomodulatory effects of HMOS and the potential role in prevention of allergic diseases. Recent studies have proposed possible mechanisms through which HMOS may contribute, either directly or indirectly, via microbiome modification, to induce oral tolerance. Future research should focus on the identification of specific pathways by which individual HMOS structures exert protective actions and thereby contribute to the capacity of the authentic HMOS mixture in early life allergy prevention.
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2.
Synthetic Oligosaccharides Mimicking Fungal Cell Wall Polysaccharides.
Krylov, VB, Nifantiev, NE
Current topics in microbiology and immunology. 2020;:1-16
Abstract
The cell wall of pathogenic fungi is highly important for the development of fungal infections and is the first cellular component to interact with the host immune system. The fungal cell wall is mainly built up of different polysaccharides representing ligands for pattern recognition receptors (PRRs) on immune cells and antibodies. Purified fungal polysaccharides are not easily available; in addition, they are structurally heterogenic and have wide molecular weight distribution that limits the possibility to use natural polysaccharides to assess the structure of their active determinants. The synthetic oligosaccharides of definite structure representing distinct polysaccharide fragments are indispensable tools for a variety of biological investigations and represent an advantageous alternative to natural polysaccharides. The attachment of a spacer group to these oligosaccharides permits their efficient transformation into immunogenic glycoconjugates as well as their immobilization on plates or microbeads. Herein, we summarize current information on synthetic availability of the variety of oligosaccharides related to main types of fungal cell wall components: galactomannan, α- and β-mannan, α- and β-(1 → 3)-glucan, chitin, chitosan, and others. These data are supplemented with published results of biochemical and immunological applications of synthetic oligosaccharides as molecular probes especially as the components of thematic glycoarrays suitable for characterization of anti-polysaccharide antibodies and cellular lectins or PRRs.
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3.
The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review.
Nolan, LS, Rimer, JM, Good, M
Nutrients. 2020;(10)
Abstract
Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.
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4.
Maternal and Infant Factors Associated with Human Milk Oligosaccharides Concentrations According to Secretor and Lewis Phenotypes.
M Tonon, K, B de Morais, M, F V Abrão, AC, Miranda, A, B Morais, T
Nutrients. 2019;(6)
Abstract
Human milk oligosaccharides (HMOs) are multifunctional carbohydrates naturally present in human milk that act as prebiotics, prevent pathogen binding and infections, modulate the immune system and may support brain development in infants. HMOs composition is very individualized and differences in HMOs concentrations may affect the infant's health. HMOs variability can be partially explained by the activity of Secretor (Se) and Lewis (Le) genes in the mother, but non-genetic maternal factors may also be involved. In this cross-sectional, observational study, 78 single human milk samples ranging from 17 to 76 days postpartum (median: 32 days, IQR: 25-46 days) were collected from breastfeeding Brazilian women, analyzed for 16 representative HMOs by liquid chromatography coupled to mass spectrometry and associations between maternal and infant factors with HMOs concentrations were investigated. HMOs concentrations presented a high variability even in women with the same SeLe phenotype and associations with maternal allergic disease, time postpartum and with infant's weight, weight gain and sex. Overall, we present unprecedented data on HMOs concentrations from breastfeeding Brazilian women and novel associations of maternal allergic disease and infant's sex with HMOs concentrations. Differences in HMOs composition attributed to maternal SeLe phenotype do not impact infant growth, but higher concentrations of specific HMOs may protect against excessive weight gain.
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5.
Effects of oligosaccharide-sialic acid (OS) compound on maternal-newborn gut microbiome, glucose metabolism and systematic immunity in pregnancy: protocol for a randomised controlled study.
Wang, S, Peng, R, Qin, S, Liu, Y, Yang, H, Ma, J
BMJ open. 2019;(9):e026583
Abstract
INTRODUCTION The gut microbiota participates in multiple human biological processes, including metabolism and immune responses. During pregnancy, the dynamics of gut microbiota is involved in physiological adaptation. The disturbed profile of microbiome is associated with maternal complications, such as gestational diabetes mellitus (GDM), which further transfers to the offspring and influence their metabolic and immunological functions in the long term. Prebiotics targeting the gut microbiota and modulating metabolic and immune functions have been shown to be effective in non-pregnant populations with metabolic syndrome. Hence, we propose the use of a prebiotic supplement, oligosaccharide-sialic acid (OS) from the first trimester until delivery in pregnant women, can benefit maternal/new-born gut microbiome, glucose metabolism and innate immunity. METHODS AND ANALYSIS In this prospective double-blinded randomised clinical trial, recruited singleton pregnancies will be stratified by body mass index (BMI) and randomly assigned to consume the OS preparation or placebo daily from the first trimester. At seven later time points (before and after recruitment in the first trimester, in the middle and third trimesters, before delivery, at birth and 42 days postpartum), compliance will be evaluated and/or biological samples will be collected. Along with maternal clinical information, questionnaires on lifestyle and infant development will be recorded. The primary outcomes are the effect of OS on the maternal-offspring gut microbiome and GDM incidence. The secondary outcomes are maternal glycolipid biochemical parameters, cytokine profiles, weight gain during pregnancy and infant morbidities, growth and development. The study aims to validate the effects of OS on reducing maternal morbidity within different BMI groups. The multiple dimensional dataset generated from the study includes clinical and lifestyle-related information, various biological markers and associated protective or risk factors for morbidity and prognosis. An extended follow-up through 42 days after birth could further explore the intrauterine influence on the long-term health of offspring. ETHICS AND DISSEMINATION This protocol has been approved by Peking University First Hospital, National Unit of Clinical Trial Ethics Committee (reference number: 164). The results are expected to be published in scientific manuscripts by 2021. TRIAL REGISTRATION NUMBER ChiCTR1800017192.
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Non-digestible carbohydrates in infant formula as substitution for human milk oligosaccharide functions: Effects on microbiota and gut maturation.
Akkerman, R, Faas, MM, de Vos, P
Critical reviews in food science and nutrition. 2019;(9):1486-1497
Abstract
Human milk (HM) is the golden standard for nutrition of newborn infants. Human milk oligosaccharides (HMOs) are abundantly present in HM and exert multiple beneficial functions, such as support of colonization of the gut microbiota, reduction of pathogenic infections and support of immune development. HMO-composition is during lactation continuously adapted by the mother to accommodate the needs of the neonate. Unfortunately, for many valid reasons not all neonates can be fed with HM and are either totally or partly fed with cow-milk derived infant formulas, which do not contain HMOs. These cow-milk formulas are supplemented with non-digestible carbohydrates (NDCs) that have functional effects similar to that of some HMOs, since production of synthetic HMOs is challenging and still very expensive. However, NDCs cannot substitute all HMO functions. More efficacious NDCs may be developed and customized for specific groups of neonates such as pre-matures and allergy prone infants. Here current knowledge of HMO functions in the neonate in view of possible replacement of HMOs by NDCs in infant formulas is reviewed. Furthermore, methods to expedite identification of suitable NDCs and structure/function relationships are reviewed as in vivo studies in babies are impossible.
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7.
Microbial production of sialic acid and sialylated human milk oligosaccharides: Advances and perspectives.
Zhang, X, Liu, Y, Liu, L, Li, J, Du, G, Chen, J
Biotechnology advances. 2019;(5):787-800
Abstract
Sialic acids (SAs) are important functional sugars, and monomers of sialylated human milk oligosaccharides (sialylated HMOs or sialyllactoses), which are crucial for improving infant development and can facilitate infant brain development, maintain brain health, and enhance immunity. The most common form of SA is N-acetylneuraminic acid (NeuAc), and the main forms of sialyllactoses are 6'-sialyllactose (6'-SL) and 3'-sialyllactose (3'-SL). As functional food additive, the demand for NeuAc and sialyllactoses will continuously increase due to their wide and important fields of application. However, NeuAc and sialyllactoses produced by traditional extraction methods are inefficient and may cause allergen contamination, and cannot keep up with the rapidly increasing market demand. Therefore, the production of NeuAc and sialyllactoses by sustainable biotechnological methods have attracted increasing attention. In particular, the development of metabolic engineering and synthetic biology techniques and strategies have promoted efficient biosynthesis of NeuAc and sialyllactoses. In this review, we first discussed the application of NeuAc and sialyllactoses. Secondly, metabolic engineering and protein engineering-fueled progress of whole-cell catalysis and de novo synthesis of NeuAc and sialyllactoses were systematically summarized and compared. Furthermore, challenges of efficient microbial production of NeuAc and sialyllactoses as well as strategies for overcoming the challenges were discussed, such as clustered regularly interspaced short palindromic repeats interference (CRISPRi)-aided identification of key precursor transport pathways, synergistically debottleneck of kinetic and thermodynamic limits in synthetic pathways, and dynamic regulation of metabolic pathways for balancing cell growth and production. We hope this review can further facilitate the understanding of limiting factors that hampered efficient production of sialic acid and sialyllactoses, as well as contribute to the development of strategies for the construction of efficient production hosts for high-level production of sialic acid and sialyllactose based on synthetic biology tools and strategies.
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Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: A systematic review.
Fernandes, R, do Rosario, VA, Mocellin, MC, Kuntz, MGF, Trindade, EBSM
Clinical nutrition (Edinburgh, Scotland). 2017;(5):1197-1206
Abstract
BACKGROUND & AIMS Studies in humans with overweight or obesity have reported that some prebiotics and synbiotics have beneficial effects on metabolic endotoxaemia and immune function. However, to date, no systematic review of controlled clinical trials assessed this topic. The aim of this study was to evaluate the effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adults with overweight or obesity. METHODS A systematic review of the literature was performed until November 6, 2015 in four electronic databases and reference lists of all included articles and relevant reviews in the field, without using any filter. RESULTS Ten trials (six prebiotic and four synbiotic trials) representing 534 overweight/obese adults were included. All trials evaluated C-reactive protein or high-sensitivity C-reactive protein, four trials evaluated cytokines (two prebiotic and two synbiotic trials) and five trials evaluated endotoxin (four prebiotic and one synbiotic trials). Six trials (two with galacto-oligosaccharide, one with inulin and three with different synbiotics) showed a reduction on high-sensitivity C-reactive protein. Four trials (one with oligofructose-enriched inulin, one with inulin and two with different synbiotics) showed a reduction on interleukin-6 and/or tumor necrosis factor. Four trials (one with galacto-oligosaccharide, one with oligofructose-enriched inulin, one with inulin and one with synbiotic) showed a reduction on endotoxin. CONCLUSIONS Some prebiotics and synbiotics may have immunomodulatory action, however, more randomized controlled trials are needed to support the clinical use of inulin-type fructans, galacto-oligosaccharides or related synbiotics for the treatment of metabolic endotoxaemia or low-grade inflammation in overweight/obese people.