BACKGROUND: The dual allergen exposure hypothesis states that sensitization to food antigens occurs through a damaged skin barrier in individuals with no previous oral tolerance to certain foods. However, the resulting allergic reaction could depend on factors such as the host's genetic predisposition as well as the skin and gut microbiota. METHODS: Specific-pathogen-free BALB/c and C57BL/6 and germ-free (GF) BALB/c mice were epicutaneously sensitized with ovalbumin (OVA) via dorsal tape-stripped skin and challenged with OVA by intragastric gavage. The development of food allergy (FA) symptoms, the Th2 and mast cell immune response and differences in the skin and gut microbiota were investigated. RESULTS: BALB/c mice, but not C57BL/6 mice, showed severe clinical signs of FA (hypothermia, diarrhea) as well as a stronger serum antibody response and Th2 cytokine secretion in the spleen and jejunum after OVA-treatment. The increased mast cell count correlated with higher MCPT-1 production and histidine decarboxylase mRNA expression in the jejunum of these mice. The 16S rRNA sequencing analysis revealed lower abundance of short-chain fatty acids producing bacteria in the gut microbiome of OVA-treated BALB/c mice. Changes in the β-diversity of the gut microbiome reflect both the genetic background as well as the OVA treatment of experimental mice. Compared to SPF mice, GF mice developed more severe anaphylactic hypothermia but no diarrhea, although they had a higher mast cell count, increased MCPT-1 production in the jejunum and serum, and increased arachidonate 5-lipoxygenase mRNA expression. CONCLUSIONS: We show that the BALB/c mice are a mouse strain of choice for model of adjuvant-free epicutaneous sensitization through the disrupted skin barrier and following food allergy development. Our results highlight the significant influence of genetic background and microbiota on food allergy susceptibility, emphasizing the complex interplay between these factors in the allergic response.

• Keywords
• epicutaneous sensitization, food allergy, germ-free, mast cells, microbiome, mouse model of allergy,
• MeSH
• Allergens immunology   MeSH
• Chymases MeSH
• Cytokines metabolism   MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Background * MeSH
• Skin * immunology   microbiology   MeSH
• Mast Cells immunology   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Ovalbumin immunology   MeSH
• Food Hypersensitivity * immunology   genetics   microbiology   MeSH
• Gastrointestinal Microbiome * immunology   MeSH
• Th2 Cells immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Allergens MeSH
• Chymases MeSH
• Cytokines MeSH
• Mcpt1 protein, mouse MeSH Browser
• Ovalbumin MeSH

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

• Keywords
• allergen immunotherapy, allergic rhinitis, asthma phenotypes and endotypes, biomarkers, food allergy,
• MeSH
• Rhinitis, Allergic * diagnosis   therapy   MeSH
• Hypersensitivity * diagnosis   therapy   MeSH
• Dermatitis, Atopic * MeSH
• Biomarkers MeSH
• Asthma * diagnosis   therapy   MeSH
• Humans MeSH
• Food Hypersensitivity * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH