Diversity of Human Milk Oligosaccharides and Effects on Early Life Immune Development

One of the well-known features of human milk, is the capacity to protect against the risk and impact of neonatal infections, as well as to influence the onset of allergic and metabolic disease manifestations. The major objective of this review is to provide a detailed overview regarding the role of human milk, more specifically the diversity in human milk oligosaccharides (HMOS), on early life immune development. Novel insights in immune modulatory effects of HMOS obtained by in vitro as well as in vivo studies, adds to the understanding on how early life nutrition may impact immune development. Extensive description and analysis of single HMOS contributing to the diversity within the composition provided during breastfeeding will be discussed with specific emphasis on immune development and the susceptibility to neonatal and childhood infections

Ovalbumin-Induced Epithelial Activation Directs Monocyte-Derived Dendritic Cells to Instruct Type 2 Inflammation in T Cells Which Is Differentially Modulated by 2'-Fucosyllactose and 3-Fucosyllactose

Allergic sensitization starts with epithelial cell activation driving dendritic cells (DCs) to instruct T helper 2 (Th2) cell polarization. Food allergens trigger intestinal epithelial cell (IEC) activation. Human milk oligosaccharides may temper the allergic phenotype by shaping mucosal immune responses.We investigated in vitro mucosal immune development after allergen exposure by combining ovalbumin (OVA)-preexposed IEC with monocyte-derived DCs (OVA-IEC-DCs) and subsequent coculture of OVA-IEC-DCs with Th cells. IECs were additionally preincubated with 2'FL or 3FL.OVA activation increased IEC cytokine secretion. OVA-IEC-DCs instructed both IL13 (p < 0.05) and IFNγ (p < 0.05) secretion from Th cells. 2'FL and 3FL permitted OVA-induced epithelial activation, but 2'FL-OVA-IEC-DCs boosted inflammatory and regulatory T-cell development. 3FL-OVA-IEC lowered IL12p70 and IL23 in DCs and suppressed IL13 (p < 0.005) in T cells, while enhancing IL17 (p < 0.001) and IL10 (p < 0.005).These results show that OVA drives Th2- and Th1-type immune responses via activation of IECs in this model. 2'FL and 3FL differentially affect OVA-IEC-driven immune effects. 2'FL boosted overall T-cell OVA-IEC immunity via DC enhancing inflammatory and regulatory responses. 3FL-OVA-IEC-DCs silenced IL13, shifting the balance towards IL17 and IL10.This model demonstrates the contribution of IEC to OVA Th2-type immunity. 2'FL and 3FL modulate the OVA-induced activation in this novel model to study allergic sensitization

Supplementation With 2′-FL and scGOS/lcFOS Ameliorates Rotavirus-Induced Diarrhea in Suckling Rats

Rotavirus (RV) is considered to be the most common cause of gastroenteritis among infants aged less than 5 years old. Human milk bioactive compounds have the ability to modulate the diarrheic process caused by several intestinal pathogens. This study aimed to evaluate the potential protective role of a specific human milk oligosaccharide, 2′-fucosyllactose (2′-FL), a mixture of the prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides 9:1 (GOS/FOS) and their combination (2′-FL+GOS/FOS) on RV-induced diarrhea in suckling rats. The nutritional intervention was performed from the second to the sixteenth day of life by oral gavage and on day 5 an RV strain was orally administered to induce infection. Fecal samples were scored daily to assess the clinical pattern of severity, incidence and duration of diarrhea. Blood and tissues were obtained at day 8 and 16 in order to evaluate the effects on the epithelial barrier and the mucosal and systemic immune responses. In the assessment of severity, incidence and duration of diarrhea, both 2′-FL and GOS/FOS displayed a beneficial effect in terms of amelioration. However, the mechanisms involved seemed to differ: 2′-FL displayed a direct ability to promote intestinal maturation and to enhance neonatal immune responses, while GOS/FOS induced an intestinal trophic effect and an RV-blocking action. The combination of 2′-FL and GOS/FOS showed additive effects in some variables. Therefore, it could be a good strategy to add these compounds in combination to infant formulas, to protect against human RV-induced diarrhea in children

Exploring Immune Development in Infants With Moderate to Severe Atopic Dermatitis

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy with a complex pathology. In adults, the clinical severity of AD has been associated with increases in T helper cell type (Th) 2, Th22, and Th17 serum markers, including high levels of CC chemokine ligand (CCL) 17 and CCL22 chemokines. Objective: To explore the possible association between serum chemokine levels and AD severity in infants with moderate-to-severe AD and elevated immunoglobulin E (IgE). Subjects and methods: Serum samples (n = 41) obtained from a randomized, double-blind, and clinical dietary intervention study were used to study biomarkers in infants with AD. Baseline- and post-intervention samples (4 months) were used, six chemokines and nine ratios thereof were analyzed using Luminex and correlated to AD severity. In the initial study, the infants were randomized to receive extensively hydrolyzed whey-based formula without (control) or with short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides (9:1) and Bifidobacterium breve M-16V (active). Results: 31 Infants up to 11 months of age, with an objective-SCORAD score (oSCORAD) ≥ 20 and elevated total-IgE and/or specific-IgE levels were included. In time, the median oSCORAD decreased in both groups by -8 (control, p < 0.05; active, p < 0.01). Irrespective of dietary intervention, several changes in Th2 chemokines (CCL17 and CCL22), inflammatory chemokine (CCL20), and the Th1 chemokine, CXC chemokine ligand (CXCL) 9, were detected over time. Overall CCL17 correlated to oSCORAD (r = 0.446, p < 0.01). After 4 months of dietary intervention, CXCL9 was higher (p < 0.01) in the active group compared with control [active, 2.33 (1.99-2.89); controls, 1.95 (1.77-2.43) log 10 median (range)]. In addition, a reduction in Th2/Th1 chemokine ratios for CCL17/CXCL9, CCL22/CXCL9, CCL20/CXCL10, and CCL20/CXCL11 was detected associated with the active intervention. Conclusion: While this study is small and exploratory in nature, these data contribute to immune biomarker profiling and understanding of AD in infants

A gastrointestinal rotavirus infection mouse model for immune modulation studies

<p>Abstract</p> <p>Background</p> <p>Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R^®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.</p> <p>Methods</p> <p>BALB/c mice were treated by gavage once daily with Gastrogard-R^®from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.</p> <p>Results</p> <p>Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R^®were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R^®. Mice receiving Gastrogard-R^®however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.</p> <p>Conclusions</p> <p>Preventing RRV-induced diarrhea by Gastrogard-R^®early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.</p

Role of Microbial Modulation in Management of Atopic Dermatitis in Children

The pathophysiology of atopic dermatitis (AD) is multifactorial and is a complex interrelationship between skin barrier, genetic predisposition, immunologic development, skin microbiome, environmental, nutritional, pharmacological, and psychological factors. Several microbial modulations of the intestinal microbiome with pre-and/or probiotics have been used in AD management, with different clinical out-come (both positive, as well as null findings). This review provides an overview of the clinical evidence from trials in children from 2008 to 2017, aiming to evaluate the effect of dietary interventions with pre-and/or pro-biotics for the treatment of AD. By searching the PUBMED/MEDLINE, EMBADE, and COCHRANE databases 14 clinical studies were selected and included within this review. Data extraction was independently conducted by two authors. The primary outcome was an improvement in the clinical score of AD severity. Changes of serum immunological markers and/or gastrointestinal symptoms were explored if available. In these studies some dietary interventions with pre-and/or pro-biotics were beneficial compared to control diets in the management of AD in children, next to treatment with emollients, and/or local corticosteroids. However, heterogeneity between studies was high, making it clear that focused clinical randomized controlled trials are needed to understand the potential role and underlying mechanism of dietary interventions in children with A

Diversity of Human Milk Oligosaccharides and Effects on Early Life Immune Development

One of the well-known features of human milk, is the capacity to protect against the risk and impact of neonatal infections, as well as to influence the onset of allergic and metabolic disease manifestations. The major objective of this review is to provide a detailed overview regarding the role of human milk, more specifically the diversity in human milk oligosaccharides (HMOS), on early life immune development. Novel insights in immune modulatory effects of HMOS obtained by in vitro as well as in vivo studies, adds to the understanding on how early life nutrition may impact immune development. Extensive description and analysis of single HMOS contributing to the diversity within the composition provided during breastfeeding will be discussed with specific emphasis on immune development and the susceptibility to neonatal and childhood infections

Immunometabolic activation of invariant natural killer T cells

Invariant natural killer T (iNKT) cells are lipid-reactive T cells with profound immunomodulatory potential. They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. In this review, we discuss the contribution of iNKT cell activation to immunometabolic disease, metabolic programming of lipid antigen presentation, and immunometabolic activation of iNKT cells. First, we outline the role of iNKT cells in immunometabolic disease. Second, we discuss the effects of cellular metabolism on lipid antigen processing and presentation to iNKT cells. The synthesis and processing of glycolipids and other potential endogenous lipid antigens depends on metabolic demand and may steer iNKT cells toward adopting a Th1 or Th2 signature. Third, external signals such as toll-like receptor ligands, adipokines, and cytokines modulate antigen presentation and subsequent iNKT cell responses. Finally, we will discuss the relevance of metabolic programming of iNKT cells in human disease, focusing on their role in disorders such as obesity and atherosclerosis. The critical response to metabolic changes places iNKT cells at the helm of immunometabolic disease

Influencing mucosal homeostasis and immune responsiveness:The impact of nutrition and pharmaceuticals

Both nutrition and orally ingested drugs pass the gastrointestinal mucosa and may affect the balance between the mucosal immune system and microbial community herein, i.e. affecting composition of the microbial community as well as the status of local immune system that controls microbial composition and maintains mucosal integrity. Numerous ways are known by which the microbial community stimulates mammalian host's immune system and vice versa. The communication between microbiota and immune system is principally mediated by interaction of bacterial components with pattern recognition receptors expressed by intestinal epithelium and various local antigen-presenting cells, resulting in activation or modulation of both innate and adaptive immune responses. Current review describes some of the factors influencing development and maintenance of a proper mucosal/immune balance, with special attention to Toll like receptor signaling and regulatory T cell development. It further describes examples (antibiotic use, HIV and asthma will be discussed) showing that disruption of the balance can be linked to immune function failure. The therapeutic potential of nutritional pharmacology herein is the main focus of discussion. (C) 2011 Elsevier B.V. All rights reserved