Microbiome and Allergy: New Insights and Perspectives.

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.

Microbiome and Allergy: New Insights and Perspectives

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies areincreasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immuneresponse to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skinmicrobiota and atopic dermatitis, and between gut microbiota and food allergy.The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics arethe techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerablyin recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased.Thus, more and more studies are proposing mechanisms for intervention in the microbiota.In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous,and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases.Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy. (AU)

El papel del microbioma en los mecanismos moleculares de las enfermedades alérgicas se ha vuelto muy relevante en los últimos años.Cada vez más estudios sugieren que una composición alterada de la microbiota, o disbiosis, puede resultar en una alteración local ysistémica de la respuesta inmune a alérgenos específicos. En este sentido, se ha establecido un vínculo entre la microbiota pulmonar y laalergia respiratoria, así como la microbiota cutánea y el desarrollo de dermatitis atópica, y la microbiota intestinal y la alergia alimentaria.La composición de la microbiota humana es dinámica y depende de diversos factores asociados al huésped como la dieta, las enfermedadesy el estilo de vida, entre otros. Para el análisis y comprensión de la microbiota, las ómicas son las técnicas de elección. En las últimasdécadas, las técnicas de análisis de microbiota han tenido un gran avance y han aumentado la necesidad de múltiples enfoques paraexplorar y comprender las enfermedades multifactoriales, incluidas las enfermedades alérgicas. De esta manera, cada vez son más losestudios que proponen mecanismos de intervención sobre la microbiota de pacientes.En esta revisión, presentamos los últimos avances encontrados en la literatura sobre la microbiota humana, centrándose en las microbiotasintestinal, cutánea y respiratoria. Discutimos la relación entre el microbioma y el sistema inmunológico, con especial énfasis en lasenfermedades alérgicas. Finalmente, discutimos las principales tecnologías para el estudio del microbioma y los estudios de intervencióndirigidos a la microbiota propuestos para la prevención de alergias. (AU)

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field.

Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

Passive transfer of antibodies to the linear epitope 60 kD Ro 273-289 induces features of Sjögren's syndrome in naive mice.

Sjögren's syndrome (SS) is an autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies to Ro60 are observed frequently in patients with SS; however, the role of these antibodies in SS initiation and progression remains unclear. The sequence Ro60 273-289 (Ro274) is a known B cell epitope of Ro60 and antibodies to this epitope have been observed in a subset of SS patients and in animals immunized with Ro60 protein. Animals immunized with Ro274 linear peptide develop a Sjögren's-like illness. We hypothesized that passive transfer of anti-Ro274-specific immunoglobulin (Ig)G would induce a Sjögren's-like phenotype. To evaluate this hypothesis, we adoptively transferred affinity-purified Ro274 antibodies into naive BALB/c animals, then evaluated salivary gland histology, function and IgG localization 4 days post-transfer. At this time-point, there was no demonstrable mononuclear cell infiltration and salivary glands were histologically normal, but we observed a functional deficit in stimulated salivary flow of animals receiving Ro274 antibodies compared to animals receiving control IgG. Cellular fractionation and enzyme-linked immunosorbent assay revealed Ro274-specific antibodies in the nucleus and cytoplasmic fractions of isolated parotid salivary gland cells that was confirmed by immunohistochemistry. These data support the hypothesis that antibodies to Ro274 deposit in salivary glands can enter intact salivary gland cells and are involved in the dysregulation of salivary flow in SS.

T-cell receptor usage in alloreactivity against HLA-B*2703 reveals significant conservation of the antigenic structure of B*2705.

B*2703 is an exceptional HLA-B27 molecule in that it differs from the most common B*2705 subtype by a unique amino acid change (His59) altering N-terminal peptide anchorage. To assess how this unusual feature affects the antigenic structure of HLA-B27, TCR usage by alloreactive CTL raised against B*2703 from two individuals was analyzed. Only few CTL recognized B*2703 from two individuals was analyzed. Only few CTL recognized B*2703 but nor ot at a lower level B*2705. Limited heterogeneity of these CTL was revealed by: 1) identity of TCR in two pairs of such CTL clones, 2) identity of beta chains, paired to distinct alpha chains, in two clonotypes, and 3) almost identical fine specificity of these two clonotypes with site-specific HLA-B27 mutants. These results indicate that B*2703 "private" epitopes are rare. TCR usage among anti-B*2703 CTL was analogous as in anti-B*2705 responses in the predominant and donor-independent usage of V beta segments from homology subgroup 4, more moderate and donor-dependent V alpha skewing, N+D beta diversity limited by motifs shared among clonotypes, and restricted J alpha heterogeneity. Homology of N+D beta motifs and J alpha segments of anti-B*2703 with anti-B*2705 TCR suggested significant sharing of peptide-associated epitopes between both subtypes. The results indicate that allospecific TCR are recruited by B*2703 following similar rules as in the anti-B*2705 response, and suggest that the B*2703 change keeps unaltered much of the antigenic structure of the molecule relative to B*2705. Therefore, most of the peptides bound to B*2703 should be the same and keep a similar conformation as in B*2705.