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Pulmonary rehabilitation: impact on salivary microbiota and immune response of people whit chronic obstrutive pulmonary disease
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Enquadramento: A doença pulmonar obstrutiva crónica (DPOC) é a terceira causa de morte mundial. A reabilitação respiratória (RR) é a terapia mais custo-efetiva para esta doença com benefícios físicos, psicológicos e socias amplamente demonstrados. Contudo, o seu impacto na microbiota não está estabelecido. Este estudo teve como objetivo investigar o efeito da RR na microbiota salivar e no perfil inflamatório de indivíduos com DPOC.
Métodos: Recrutaram-se dois grupos de participantes, o grupo experimental-GE (n=38) que realizou RR comunitária durante 12 semanas e o grupo controlo-GC (n=38) que não foi submetido a nenhuma intervenção adicional. Foram recolhidos dados clínicos (e.g., impacto da doença e dispneia) antes e imediatamente após RR e amostras mensais de saliva durante 6 meses. Os 2 grupos foram emparelhados para idade, género, índice de massa corporal, volume expiratório máximo num segundo percentagem do previsto (FEV1pp) e hábitos tabágicos. Os perfis da microbiota e inflamatórios das amostras de saliva foram determinados através da sequenciação do gene 16S rRNA e através da quantificação de citocinas inflamatórias, IgA secretado (SIgA) e proteína total, respetivamente. Modelos Lineares Mistos foram usados para avaliar as dinâmicas da microbiota ao longo do tempo. As análises de abundância diferencial foram conduzidas de forma direcionada para Proteobacteria, Bacteroidetes, Haemophilus e Prevotella. Alfa e beta diversidades foram estimadas com os índices filogenético e Shannon e a distância Weighted Unifrac, respetivamente. Regressões logísticas foram aplicadas para determinar a associação entre a microbiota antes da RR e a resposta dos doentes aos domínios clínicos. A variação da concentração das citocinas e SIgA ao longo do tempo foram avaliadas com o teste de Friedman.
Resultados: Participaram setenta e seis indivíduos com DPOC (grupo controlo: 31 homens, 70±7.6 anos, FEV1pp 52.3±19.8 e grupo experimental: 29 homens, 72±9 anos, FEV1pp 49.2±16). A microbiota do grupo experimental mudou significativamente face ao grupo controlo (p<0.0001). A RR pareceu reduzir a heterogeneidade da composição da microbiota. A maioria dos doentes submetidos à RR apresentou um aumento significativo de Proteobacteria (p=0.00070) e Haemophilus (p=0.019), bem como, diminuição de Bacteroidetes (p=0.030) e Prevotella (p=0.013). Não foram observadas alterações significativas no grupo controlo. A diversidade da microbiota em resposta à RR não se alterou significativamente. Verificou-se uma associação entre a composição da microbiota antes da RR e o impacto da doença e a dispneia. Durante e imediatamente após a RR, os doentes apresentaram um aumento significativo de IL-1β (p=0.041) e TNF-α (p=0.041), respetivamente; contudo, não foram observadas diferenças na SIgA.
Conclusões: O nosso estudo sugere que a RR modula a microbiota salivar e o perfil inflamatório de pessoas com DPOC. A curto prazo, a microbiota parece aproximar-se do perfil característico da DPOC grave devido ao aumento de Proteobacteria e diminuição de Bacteroidetes. Uma resposta pro-inflamatória à RR parece ocorrer devido ao aumento de IL-1β e TNF-α. Novos estudos são necessários para melhor caracterizar as alterações na microbiota salivar e resposta inflamatória induzidas pela RR.
Background: Chronic obstructive pulmonary disease (COPD) is the third world leading cause of death. Pulmonary rehabilitation (PR) is the most cost-effective therapy for this disease with physical, psychological, and social benefits widely demonstrated. Nevertheless, its impact on the microbiota has not been established. This study aimed to investigate the effect of PR in the salivary microbiota and inflammatory profile of people with COPD. Methods: Two groups of participants were recruited, the experimental group-EG (n=38) that performed community-based PR for 12-weeks and the control group-CG (n=38) that was not submitted to any additional intervention. Clinical data were collected (e.g., the impact of disease and dyspnoea) prior and immediately after PR, and monthly saliva samples for 6 months. The 2 groups were matched for age, sex, body mass index, forced expiratory volume in 1 second (FEV1pp), and pack-years. Microbiota and inflammatory profiles of saliva samples were determined through 16S rRNA gene sequencing and quantification inflammatory cytokines, secretory IgA (SIgA) and total protein, respectively. Liner Mixed Models were used to evaluate microbiota dynamics over time. Differential abundance analyses were targeted to Proteobacteria, Bacteroidetes, Haemophilus, and Prevotella. Alpha and beta diversities were estimated with phylogenetic and Shannon indexes and Weighted Unifrac distance, respectively. Logistic regressions were applied to explore the association among microbiota before PR and patients’ response to clinical domains. Variation of cytokines and SIgA concentrations over time were assessed with Friedman test. Results: Seventy-six individuals with COPD participated (control group: 31 male, 70±7.6y, FEV1pp 52.3±19.8 and experimental group: 29 male, 72±9y, FEV1pp 49.2±16). The microbiota of the experimental group changed significantly over time compared to the control group (p<0.0001). PR seemed to reduce the heterogeneity of the microbiota composition. Most patients submitted to PR presented a significant increase in Proteobacteria (p=0.00070) and Haemophilus (p=0.019) as well as a decrease in Bacteroidetes (p=0.030) and Prevotella (p=0.013). No significant differences were observed in the control group. The microbiota diversity in response to PR did not change significantly. There was an association between the microbiota composition before PR and the impact of the disease and dyspnoea. During and immediately after PR, patients presented a significant increase in IL-1β (p=0.041) and TNF-α (p=0.041), respectively; however, no significant differences were observed regarding SIgA. Conclusions: Our study suggests that PR modulates the salivary microbiota and the inflammatory profile of people with COPD. In short term, the microbiota composition seems to become closer to the profile characteristic of severe COPD due to the increase in Proteobacteria and the decrease in Bacteroidetes. A pro-inflammatory response to PR also seems to occur due to the increase in IL-1β and TNF-α. Further studies are needed to further explore the effects of PR in microbiota composition and inflammatory response in COPD context.
Background: Chronic obstructive pulmonary disease (COPD) is the third world leading cause of death. Pulmonary rehabilitation (PR) is the most cost-effective therapy for this disease with physical, psychological, and social benefits widely demonstrated. Nevertheless, its impact on the microbiota has not been established. This study aimed to investigate the effect of PR in the salivary microbiota and inflammatory profile of people with COPD. Methods: Two groups of participants were recruited, the experimental group-EG (n=38) that performed community-based PR for 12-weeks and the control group-CG (n=38) that was not submitted to any additional intervention. Clinical data were collected (e.g., the impact of disease and dyspnoea) prior and immediately after PR, and monthly saliva samples for 6 months. The 2 groups were matched for age, sex, body mass index, forced expiratory volume in 1 second (FEV1pp), and pack-years. Microbiota and inflammatory profiles of saliva samples were determined through 16S rRNA gene sequencing and quantification inflammatory cytokines, secretory IgA (SIgA) and total protein, respectively. Liner Mixed Models were used to evaluate microbiota dynamics over time. Differential abundance analyses were targeted to Proteobacteria, Bacteroidetes, Haemophilus, and Prevotella. Alpha and beta diversities were estimated with phylogenetic and Shannon indexes and Weighted Unifrac distance, respectively. Logistic regressions were applied to explore the association among microbiota before PR and patients’ response to clinical domains. Variation of cytokines and SIgA concentrations over time were assessed with Friedman test. Results: Seventy-six individuals with COPD participated (control group: 31 male, 70±7.6y, FEV1pp 52.3±19.8 and experimental group: 29 male, 72±9y, FEV1pp 49.2±16). The microbiota of the experimental group changed significantly over time compared to the control group (p<0.0001). PR seemed to reduce the heterogeneity of the microbiota composition. Most patients submitted to PR presented a significant increase in Proteobacteria (p=0.00070) and Haemophilus (p=0.019) as well as a decrease in Bacteroidetes (p=0.030) and Prevotella (p=0.013). No significant differences were observed in the control group. The microbiota diversity in response to PR did not change significantly. There was an association between the microbiota composition before PR and the impact of the disease and dyspnoea. During and immediately after PR, patients presented a significant increase in IL-1β (p=0.041) and TNF-α (p=0.041), respectively; however, no significant differences were observed regarding SIgA. Conclusions: Our study suggests that PR modulates the salivary microbiota and the inflammatory profile of people with COPD. In short term, the microbiota composition seems to become closer to the profile characteristic of severe COPD due to the increase in Proteobacteria and the decrease in Bacteroidetes. A pro-inflammatory response to PR also seems to occur due to the increase in IL-1β and TNF-α. Further studies are needed to further explore the effects of PR in microbiota composition and inflammatory response in COPD context.
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Palavras-chave
Doença pulmonar obstrutiva crónica Reabilitação respiratória Microbiologia celular Resposta inflamatória