Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma

BACKGROUND: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. OBJECTIVE: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. METHODS: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. RESULTS: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. CONCLUSION: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration

Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-28T19:15:53Z No. of bitstreams: 1 Fiuza BS Polymorphisms in DENND1B gene are associated....pdf: 785468 bytes, checksum: 752a3a4da4f9e5c39c215f56d208c14b (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-28T19:25:21Z (GMT) No. of bitstreams: 1 Fiuza BS Polymorphisms in DENND1B gene are associated....pdf: 785468 bytes, checksum: 752a3a4da4f9e5c39c215f56d208c14b (MD5)Made available in DSpace on 2018-02-28T19:25:21Z (GMT). No. of bitstreams: 1 Fiuza BS Polymorphisms in DENND1B gene are associated....pdf: 785468 bytes, checksum: 752a3a4da4f9e5c39c215f56d208c14b (MD5) Previous issue date: 2017CNPq − National Research Council - Brazil and FAPESB − State of Bahia, Brazil Research CouncilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, BrasilUniversidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, BrasilAsthma is a heterogeneous disease associated with a complex basis involving environmental factors and individual variabilities. The DENN Domain Containing 1B (DENND1B) gene has an important role on T cell receptor (TCR) down-regulation on Th2 cells and studies have shown that mutations or loss of this factor can be associated with increased Th2 responses and asthma. The aim of this work is to evaluate the association of polymorphisms in the DENND1B with asthma and allergy markers phenotypes in Brazilian children. Genotyping was performed using a commercial panel from Illumina (2.5 Human Omni bead chip) in 1309 participants of SCAALA (Social Change, Asthma, Allergy in Latin American) program. Logistic regressions for asthma and atopy markers were performed using PLINK software 1.9. The analyzes were adjusted for sex, age, helminth infections and ancestry markers. The DENND1B gene was associated with different phenotypes such as severe asthma and atopic markers (specific IgE production, skin prick test and IL-13 production). Among the 166 SNPs analyzed, 72 were associated with asthma and/or allergy markers. In conclusion, polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma

Variants in the IL17 pathway genes are associated with atopic asthma and atopy makers in a South American population

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-27T18:49:19Z No. of bitstreams: 1 Silva, J. M. Variants_in_the_IL17_.pdf: 1261480 bytes, checksum: c76565f612715004421e85c96914b33a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-09-27T18:59:41Z (GMT) No. of bitstreams: 1 Silva, J. M. Variants_in_the_IL17_.pdf: 1261480 bytes, checksum: c76565f612715004421e85c96914b33a (MD5)Made available in DSpace on 2019-09-27T18:59:41Z (GMT). No. of bitstreams: 1 Silva, J. M. Variants_in_the_IL17_.pdf: 1261480 bytes, checksum: c76565f612715004421e85c96914b33a (MD5) Previous issue date: 2019National Research Ethics Committee (reference number: 120.616) and free informed consent was properly obtained from the parents or legal guardian of each child.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Departamento de Ciências da Biointeração. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Universidade Federal da Bahia. Instituto de Ciências da Saúde. Laboratório de Imunofarmacologia e Biologia Molecular. Departamento de Biorregulação. Salvador, BA, Brasil.Asthma is a complex disorder with multiple phenotypes which can influence its severity and response to treatment. The TH17 lymphocytes producing IL-17A and IL17-F cytokines, may have a role on asthma inflammation. The aim of our study was to evaluate the association between genetic variants in IL17 pathway genes with asthma and atopy markers. Materials and methods: Genotyping was performed using a commercial panel in 1245 participants of SCAALA cohort. The study included 91 SNVs in IL-17 pathway genes. Logistic regressions for asthma and atopy markers were performed using PLINK 1.9. In silico analyses were performed using rSNPbase, RegulomeDB, and Gtex portal for in silico gene expression. Results and discussion: The T allele of rs1974226 in IL17A was positively associated with asthma (OR: 1.37; 95% CI 1.02–1.82). Also, the T allele of rs279548 was positively associated with asthma (OR: 1.30; 95% CI 1.02–1.64), atopy (OR: 1.62; 95% CI 1.05–2.50) and increased expression of the IL17RC in lung and whole blood tissues. The others genetic variants in the IL17 pathways genes were associated with both protection and risk for asthma development as well as with IgE levels. Conclusion: The genetic variants in IL-17-related genes are associated with the atopic asthma phenotype and IgE production

Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:49:50Z No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-08-16T11:59:43Z (GMT) No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5)Made available in DSpace on 2018-08-16T11:59:43Z (GMT). No. of bitstreams: 1 Pires AO Polymorphisms in the DAD1 and OXA1L....pdf: 1226142 bytes, checksum: c0fa5af323611b005d0a4abe202c2c33 (MD5) Previous issue date: 2018Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado da Bahia (FAPESB).Federal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Allergy and Acarology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFederal University of Bahia. Laboratory of Immunopharmacology and Molecular Biology. Salvador, BA, BrazilAtopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome-wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2-type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over-expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma