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

Profile of the intestinal microbiota in asthmatic individuals and its immunomodulatory role

The phenomenon of dysbiosis in the intestinal microbiome can influence the host's immune development and the incidence of allergic diseases. It is believed that microbiome-host interactions, i.e., symbiosis, contribute to the proper development of the immune system, while microbial dysbiosis has been associated with a variety of inflammatory disorders, including asthma. The aim of this study is to characterize the taxonomic profile of the intestinal microbiota in asthmatic individuals participating in the World Asthma Phenotypes (WASP) and associate it with related immunomodulatory mechanisms. The assessment of the intestinal microbiota was conducted through sequencing the V4 region of the 16S rRNA gene from bacterial DNA extracted from stool samples, followed by bioinformatic analysis using the QIIME2 software. Association with the immune response was investigated using markers such as skin prick test positivity, induced sputum cellularity, and cytokine levels in nasal lavage. Although all predominant phyla, such as Tenericutes, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, were consistent between asthmatics and non-asthmatics, differences in relative abundances were observed. No significant differences in bacterial richness or diversity were identified between asthmatics and non-asthmatics based on alpha diversity. However, a statistically significant dissimilarity in beta diversity was observed. The genus Bacteroides was the most abundant, contributing to the dissimilarity within the asthmatic group, while Prevotella was more prevalent in non-asthmatics. The presence of Bacteroides in the microbiota of asthmatics correlated with IL-4 production in nasal lavage. These results reinforce the understanding of differences in the microbial community between asthmatic and non-asthmatic individuals.Fundação de Amparo à Pesquisa do Estado da BahiaEuropean Research CouncilO fenômeno da disbiose no microbioma intestinal pode influenciar o desenvolvimento imunológico do hospedeiro e a incidência de doenças alérgicas. Acredita-se que as interações microbioma-hospedeiro, ou seja, a simbiose, contribuam para o desenvolvimento adequado do sistema imunológico, enquanto a disbiose microbiana tem sido associada a uma variedade de distúrbios inflamatórios, incluindo a asma. O objetivo deste estudo é caracterizar o perfil taxonômico da microbiota intestinal de indivíduos asmáticos, participantes do World Asthma Phenotypes (WASP), e associá-lo a mecanismos imunomoduladores associados. A avaliação da microbiota intestinal foi realizada a partir do sequenciamento da região V4 do gene 16S rRNA do DNA bacteriano extraído de amostras de fezes, seguido de análise de bioinformática no software QIIME2. A associação com a resposta imune foi realizada utilizando marcadores como a positividade ao teste cutâneo, celularidade do escarro induzido e dosagem de citocinas no lavado nasal. Embora todos os filos predominantes, como Tenericutes, Proteobacteria, Firmicutes, Bacteroidetes e Actinobacteria, tenham sido consistentes entre asmáticos e não asmáticos, observaram-se diferenças nas abundâncias relativas. Não foram identificadas diferenças significativas na riqueza ou diversidade bacteriana entre asmáticos e não asmáticos, com base na diversidade alfa. No entanto, uma dissimilaridade estatisticamente significativa na diversidade beta foi observada. O gênero Bacteroides destacou-se como o mais abundante, contribuindo para a dissimilaridade entre o grupo asmático, enquanto Prevotella foi mais prevalente em não asmáticos. A presença de Bacteroides na microbiota dos asmáticos correlacionou-se com a produção de IL-4 no lavado nasal. Esses resultados reforçam a compreensão das diferenças na comunidade microbiana entre indivíduos asmáticos e não asmáticos

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

Pharmacovigilance in Vaccines: Importance, Main Aspects, Perspectives, and Challenges—A Narrative Review

Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain

High-Content Imaging-Based Assay for SARS-CoV-2-Neutralizing Antibodies

The COVID-19 pandemic and the consequent emergence of new SARS-CoV-2 variants of concern necessitates the determination of populational serum potency against the virus. Here, we standardized and validated an imaging-based method to quantify neutralizing antibodies against lentiviral particles expressing the spike glycoprotein (pseudovirus). This method was found to efficiently quantify viral titers based on ZsGreen-positive cells and detect changes in human serum neutralization capacity induced by vaccination with up to two doses of CoronaVac, Comirnaty, or Covishield vaccines. The imaging-based protocol was also used to quantify serum potency against pseudoviruses expressing spikes from Delta, Omicron BA.1.1.529, and BA.4/5. Our results revealed increases in serum potency after one and two doses of the vaccines evaluated and demonstrated that Delta and Omicron variants escape from antibody neutralization. The method presented herein represents a valuable tool for the screening of antibodies and small molecules capable of blocking viral entry and could be used to evaluate humoral immunity developed by different populations and for vaccine development

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