Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70–80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured.

Food allergy is an aberrant immune-mediated reaction against harmless food substances, such as cow’s milk proteins. Due to its very early introduction, cow’s milk allergy is one of the earliest and most common food allergies. For this reason cow’s milk allergy can be recognized as one of the first indications of an aberrant inflammatory response in early life. Classically, cow’s milk allergy, as is true for most other allergies as well, is primarily associated with abnormal humoral immune responses, that is, elevation of specific immunoglobulin E levels. There is growing evidence indicating that cellular components of both innate and adaptive immunity play significant roles during the pathogenesis of cow’s milk allergy. This is true for the initiation of the allergic phenotype (stimulation and skewing towards sensitization), development and outgrowth of the allergic disease. This review discusses findings pertaining to roles of cellular immunity in allergic inflammation, and tolerance induction against cow’s milk proteins. In addition, a possible interaction between immune mechanisms underlying cow’s milk allergy and other types of inflammation (infections and noncommunicable diseases) is discussed.

Summary: Background: Failure to induce oral tolerance may result in food allergy. Hydrolysed cow's milk‐based infant formulas are recommended in subjects with a high risk of developing allergic disease. Presentation of T cell epitopes is a prerequisite to generate regulatory T cells that could contribute to oral tolerance.Objective: To investigate whether a specific hydrolysed whey‐based infant formula contains peptides that function as T cell epitopes to support the development of oral tolerance to whey.Methods: First, a novel liquid chromatography‐mass spectrometry (LC‐MS) method was developed to characterize β‐lactoglobulin‐derived peptides present in a specific infant formula with a focus on region AA#13‐48 of β‐lactoglobulin, which has previously been described to contain T cell epitopes with tolerogenic potential. Second, the formula was subjected to the ProImmune ProPresent^® antigen presentation assay and MHC class II binding algorithm to identify relevant HLA‐DRB1‐restricted peptides. Third, identified peptides were tested on human cow's milk protein‐specific T cell lines to determine T cell recognition.Results: Thirteen peptides of minimal 9AAs long that overlap with AA#13‐48 of β‐lactoglobulin were identified. Six of them were found across all batches analysed. It was further confirmed that these peptides were processed and presented by human dendritic cells. The identified HLA‐DRB1‐restricted peptides were correlated to AA#11‐30 and AA#23‐39 of β‐lactoglobulin. Importantly, the proliferation assay showed that the synthetic peptides were recognized by cow's milk protein‐specific T cell lines and induced T cell proliferation.Conclusion and Clinical Relevance: This study demonstrates that the tested hydrolysed infant formula contains functional HLA‐DRB1‐restricted T cell epitopes, which can potentially support the development of oral tolerance to whey.

Background. In previous studies, we showed that a fructo-oligosaccharide- (FOS-) supplemented diet enhanced oral immunotherapy (OIT) efficacy in a mouse model for cow’s milk allergy. Fermentation of FOS by intestinal bacteria leads to production of short-chain fatty acids (SCFA) including butyrate.Aim. To investigate the contribution of butyrate in the enhanced efficacy of OIT + FOS.Methods. C3H/HeOuJ mice were sensitized and received OIT with or without FOS or butyrate supplementation. After treatment, whole blood was collected to conduct a basophil activation test (BAT) and allergen challenges were performed to measure acute allergic symptoms. CD4 + CD25 + regulatory T cells (Tregs) were isolated from treated mice or differentiatedin vitroand used in a bone marrow-derived mast cell (BMMC) suppression assay. Cecum content was collected to analyze SCFA concentrations.Results. Allergen-induced basophil activation was reduced in OIT + butyrate samples compared to OIT. Accordingly, the acute allergic skin response and mast cell degranulation upon challenge were reduced in OIT + butyrate and OIT + FOS mice compared to sensitized controls. Butyrate was increased in the cecum content of OIT + FOS mice compared to OIT mice and sensitized controls. Treg-mediated BMMC suppression was enhanced afterin vivobutyrate and FOS exposure in combination with OIT but with a more pronounced effect for butyrate.Conclusion. Butyrate supplementation enhanced OIT-induced desensitization of basophils and mast cells and Treg functionality. Only OIT + FOS treatment induced potential microbial alterations, shown by increased butyrate levels in cecum content. Both butyrate and FOS are promising candidates to improve OIT efficacy in human studies to treat food allergies.