Immunoglobulin E (IgE)‐mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. Exposure to even minute quantities of allergens can lead to the ...production of IgE antibodies in atopic individuals. This is termed allergic sensitization, which occurs mainly in early childhood. Allergen‐specific IgE then binds to the high (FcεRI) and low‐affinity receptors (FcεRII, also called CD23) for IgE on effector cells and antigen‐presenting cells. Subsequent and repeated allergen exposure increases allergen‐specific IgE levels and, by receptor cross‐linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE‐facilitated allergen presentation perpetuates T cell–mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE, even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen‐specific IgG and IgA antibodies usually recognize different epitopes on allergens compared with IgE and do not efficiently interfere with allergen‐induced inflammation. However, IgG and IgA antibodies to these important IgE epitopes can be induced by allergen‐specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti‐IgE treatment does the same by preventing IgE from binding to its receptor on mast cells and basophils. Here, we review the complex interplay of allergen‐specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.
Aim
To evaluate the ability of specific carbohydrates, including commercially available products, to support the growth of representatives of two well‐known groups of gut commensals, namely ...lactobacilli and bifidobacteria.
Methods and Results
Sixty‐eight bacterial strains, representing 29 human‐derived lactobacilli and 39 bifidobacteria (both human‐ and animal‐derived), were tested for their ability to metabolize 10 different carbohydrates. Analysis of growth and metabolic activity was performed using a combination of diagnostic parameters, such as final OD600, final pH, fermentation end products and growth rate.
Conclusions
The data assembled in this study provide significant complementary and comparative information on the growth‐promoting properties of a range of carbohydrates, while also investigating interspecies differences between lactobacilli and/or bifidobacteria with regard to their carbohydrate utilization abilities. Galacto‐oligosaccharides (GOS) and lactulose were shown to support the most favourable growth characteristics, whereas relatively poor growth of lactobacilli and bifidobacteria was observed on inulin, maltodextrin and polydextrose. GOS/inulin (9 : 1) and fructo‐oligosaccharides (FOS)/inulin mixtures supported mostly similar growth abilities to those obtained for GOS and FOS, respectively. Microbial consumption of GOS, as determined by high‐performance anion‐exchange chromatography with pulsed amperometric detection, was evident for both lactobacilli and bifidobacteria.
Significance and Impact of the Study
These results may allow for the rational prediction of lactobacilli and/or bifidobacteria to be used in conjunction with prebiotics, such as GOS, as synbiotics.
Human milk oligosaccharides (HMOs) comprise a group of structurally complex, unconjugated glycans that are highly abundant in human milk. HMOs are minimally digested in the gastrointestinal tract and ...reach the colon intact, where they shape the microbiota. A small fraction of HMOs is absorbed, reaches the systemic circulation, and is excreted in urine. HMOs can bind to cell surface receptors expressed on epithelial cells and cells of the immune system and thus modulate neonatal immunity in the infant gut, and possibly also sites throughout the body. In addition, they have been shown to act as soluble decoy receptors to block the attachment of various microbial pathogens to cells. This review summarizes the current knowledge of the effects HMOs can have on infections, allergies, auto-immune diseases and inflammation, and will focus on the role of HMOs in altering immune responses through binding to immune-related receptors.
Specific and adequate nutrition during pregnancy and early life is an important factor in avoiding non-communicable diseases such as obesity, type 2 diabetes, cardiovascular disease, cancers, and ...chronic allergic diseases. Although epidemiologic and experimental studies have shown that nutrition is important at all stages of life, it is especially important in prenatal and the first few years of life. During the last decade, there has been a growing interest in the potential role of epigenetic mechanisms in the increasing health problems associated with allergic disease. Epigenetics involves several mechanisms including DNA methylation, histone modifications, and microRNAs which can modify the expression of genes. In this study, we focus on the effects of maternal nutrition during pregnancy, the effects of the bioactive components in human and bovine milk, and the environmental factors that can affect early life (i.e., farming, milk processing, and bacterial exposure), and which contribute to the epigenetic mechanisms underlying the persistent programming of immune functions and allergic diseases. This knowledge will help to improve approaches to nutrition in early life and help prevent allergies in the future.
Background Farm milk consumption has been identified as an exposure that might contribute to the protective effect of farm life on childhood asthma and allergies. The mechanism of action and the role ...of particular constituents of farm milk, however, are not yet clear. Objective We sought to investigate the farm milk effect and determine responsible milk constituents. Methods In rural regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about farm milk consumption and other farm-related exposures was completed by parents of 8334 school-aged children, and 7606 of them provided serum samples to assess specific IgE levels. In 800 cow's milk samples collected at the participants' homes, viable bacterial counts, whey protein levels, and total fat content were analyzed. Asthma, atopy, and hay fever were associated to reported milk consumption and for the first time to objectively measured milk constituents by using multiple regression analyses. Results Reported raw milk consumption was inversely associated to asthma (adjusted odds ratio aOR, 0.59; 95% CI, 0.46-0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI, 0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a protective effect. Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy. Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30-0.97), α-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and β-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39-0.97), however, were inversely associated with asthma but not with atopy. Conclusions The findings suggest that the protective effect of raw milk consumption on asthma might be associated with the whey protein fraction of milk.
Ageing is associated with a changing immune system, leading to inflammageing (increased levels of inflammation markers in serum) and immunosenescence (reduced immune cells and reduced responses ...towards pathogens). This results in reduced vaccination responses and increased infections in elderly. Much is known about the adaptive immune system upon ageing, but less is known about the innate immune system. Therefore, the aim of this study was to compare innate immune function of Toll like receptor (TLR)-mediated responses between elderly and young adult women. To this end, elderly and young adult women were compared to study the effect of ageing on the relative prevalence and reactivity to TLR-mediated responses of myeloid- and plasmacytoid dendritic cells (mDC, pDC). In addition, TLR expression and inflammatory markers in serum were investigated. Elderly women had reduced numbers of circulating pDCs. In addition, pDCs and mDCs of elderly women responded differently towards TLR stimulation, especially TLR7/8 mediated stimulation was reduced, compared to young adults. In serum, markers involved in inflammation were generally increased in elderly. In conclusion, this study confirms and extends the knowledge about immunosenescence and inflammageing on innate immunity in elderly women.
The experimental challenge with attenuated enterotoxigenic E. coli strain E1392/75-2A prevents diarrhea upon a secondary challenge with the same bacteria. A dose-response pilot study was performed to ...investigate which immunological factors are associated with this protection. Healthy subjects were inoculated with increasing E. coli doses of 1E6-1E10 CFU, and three weeks later, all participants were rechallenged with the highest dose (1E10 CFU). Gastrointestinal discomfort symptoms were recorded, and stool and blood samples were analyzed. After the primary challenge, stool frequency, diarrhea symptom scores, and E. coli-specific serum IgG (IgG-CFA/II) titer increased in a dose-dependent manner. Fecal calprotectin and serum IgG-CFA/II response after primary challenge were delayed in the lower dose groups. Even though stool frequency after the secondary challenge was inversely related to the primary inoculation dose, all E. coli doses protected against clinical symptoms upon rechallenge. Ex vivo stimulation of PBMCs with E. coli just before the second challenge resulted in increased numbers of IL-6+/TNF-α+ monocytes and mDCs than before the primary challenge, without dose-dependency. These data demonstrate that primary E. coli infection with as few as 1E6 CFU protects against a high-dose secondary challenge with a homologous attenuated strain. Increased serum IgG-CFA/II levels and E. coli-induced mDC and monocyte responses after primary challenge suggest that protection against secondary E. coli challenges is associated with adaptive as well as innate immune responses.
During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained ...by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and
which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms
which cow's milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.
Intake of dietary advanced glycation end products (AGEs) is associated with inflammation-related health problems. Nε-carboxymethyl lysine (CML) is one of the best characterised AGEs in processed ...food. AGEs have been described as ligands for receptors present on antigen presenting cells. However, changes in protein secondary and tertiary structure also induce binding to AGE receptors. We aimed to discriminate the role of different protein modifications in binding to AGE receptors. Therefore, β-lactoglobulin was chemically modified with glyoxylic acid to produce CML and compared to β-lactoglobulin glycated with lactose. Secondary structure was monitored with circular dichroism, while hydrophobicity and formation of β-sheet structures was measured with ANS-assay and ThT-assay, respectively. Aggregation was monitored using native-PAGE. Binding to sRAGE, CD36, and galectin-3 was measured using inhibition ELISA. Even though no changes in secondary structure were observed in all tested samples, binding to AGE receptors increased with CML concentration of CML-modified β-lactoglobulin. The negative charge of CML was a crucial determinant for the binding of protein bound CML, while binding of glycated BLG was determined by increasing hydrophobicity. This shows that sRAGE, galectin-3, and CD36 bind to protein bound CML and points out the role of negatively charged AGEs in binding to AGE receptors.
Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default ...response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.
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