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

Avaliação de polimorfismos nos genes FOXO3A, AMPK EPOMC e sua relação com a obesidade mórbida

Exportado OPUSMade available in DSpace on 2019-08-11T01:56:25Z (GMT). No. of bitstreams: 1 disserta__o_cvns_ufmg_2013.pdf: 2318736 bytes, checksum: aa3f5ed3fe5d59ec71b8dd5fe0a48470 (MD5) Previous issue date: 18A obesidade mórbida (OBM) é um distúrbio metabólico comum na população mundial. A doença representa um alto risco para a saúde já que, frequentemente, encontra-se associada a diversas comorbidades, como doenças cardiovasculares e diabetes tipo 2. Além de fatores ambientais, diversos estudos também têm sugerido que determinados polimorfismos genéticos predispõem ao desenvolvimento da OBM. Os genes FOXO3a (fator de transcrição forkhead box O 3a), AMPK (proteína quinase ativada por AMP) e POMC (proopiomelanocortina) codificam proteínas reguladoras do metabolismo energético e comportamento alimentar e, desta forma, é possível que suas variantes genéticas possam modular a susceptibilidade à OBM. Por esse motivo, os polimorfismos dos genes FOXO3a (rs1536057, rs2802292, rs3813498, rs1935952), AMPK (rs1442760, rs1036851, rs1348316, rs11584787) e POMC (rs934778, rs6545975) foram investigados a fim de conferir o risco de desenvolver OBM. Para tanto, foram recrutados 242 pacientes obesos mórb idos (IMC 40 Kg/m²) e 283 indivíduos saudáveis (IMC 24,99 Kg/m²). Em seguida, os polimorfismos de interesse foram avaliados através do método TaqMan Genotypinga partir de DNA isolado do sangue. As análises genéticas do estudo demonstraram que as frequências alélicas e genotípicas de quatro dos polimorfismos estudados, a saber, rs1536057 (FOXO3a), rs103685 (AMPK), rs934778 e rs6545975 (POMC), foram distribuídas diferentemente entre os grupos de obesos mórbidos e indivíduos saudáveis. Nenhuma associação significativa foi encontrada quando as análises de interação gene-gene foram empregadas. Os resultados deste estudo fornecem dados inéditos sobre a frequência genética dos marcadores estudados na população brasileira e sustentam o princípio de que variações genéticas específicas podem conferir o risco de desenvolver a OBM.Morbid obesity (MO) is a metabolic disorder that affects people worldwide. Excessive fat accumulation in MO patients is frequently found to increase the risk for several co-morbidities, including cardiovascular disease and type 2 diabetes. Although environmental factors are well-known to play a role in MO risk, accumulate evidence has also highlighted that inherited factors may predispose subjects to MO. Because the genes FOXO3a (forkhead box O 3a transcription factor), AMPK (activated protein kinase) and POMC (proopiomelanocortin) encode regulatory proteins that act on both energy metabolism and feeding beha vior, here we have addressed whether polymorphisms in these genes are risk factors to MO. Therefore, the genetic frequencies of rs1536057, rs2802292, rs3813498, rs1935952 (FOXO3a), rs1442760, rs1036851, rs1348316, rs11584787 (AMPK ) and rs934778, rs6545975 (POMC) were evaluated in 242 morbidly obese patients (BMI 40 kg/m²) and 283 healthy subjects (BMI 24.99 kg/m²). DNA samples were isolated from blood and genotyping was performed by TaqMan-based assays. Our findings revealed that out of 10 polymorphisms analyzed, only allele and genotype frequencies of rs1536057 (FOXO3a), rs103685 (AMPK), rs934778 and rs6545975 (POMC) were heterogeneously distributed between morbid obesity and healthy subjects groups. Furthermore, epistasis analysis did not show any significant model of genetic interaction influencing the susceptibility to morbid obesity. Results of this study for the first time provide data on distribution of FOXO3a, AMPK and POMC polymorphisms in the Brazilian population and suggest that selected geneti c variants may confer risk of morbid obesity in humans

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma

Objectives: The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. Methods: A total of 1066 adults were evaluated. Asthma and chronic⁄allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. Results: Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p = 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27–3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80–3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27–3.50). Conclusion: Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. Level of evidence: Level 3