Responsiveness to pulmonary rehabilitation in COPD is associated with changes in microbiota.

BACKGROUND: Pulmonary Rehabilitation (PR) is one of the most cost-effective therapies for chronic obstructive pulmonary disease (COPD) management. There are, however, people who do not respond to PR and reasons for non-response are mostly unknown. PR is likely to change the airway microbiota and this could play a role in its responsiveness. In this study we have explored the association between PR effectiveness and specific alterations in oral microbiota and inflammation. METHODS: A prospective longitudinal study was conducted. Data on exercise capacity, dyspnoea, impact of disease and 418 saliva samples were collected from 76 patients, half of whom participated in a 12-weeks PR programme. Responders and non-responders to PR (dyspnoea, exercise-capacity and impact of disease) were defined based on minimal clinically important differences. RESULTS: Changes in microbiota, including Prevotella melaninogenica and Streptococcus were observed upon PR. Prevotella, previously found to be depleted in severe COPD, increased during the first month of PR in responders. This increase was negatively correlated with Streptococcus and Lautropia, known to be enriched in severe cases of COPD. Simultaneously, an anti-inflammatory commensal of the respiratory tract, Rothia, correlated strongly and negatively with several pro-inflammatory markers, whose levels were generally boosted by PR. Conversely, in non-responders, the observed decline in Prevotella correlated negatively with Streptococcus and Lautropia whose fluctuations co-occurred with several pro-inflammatory markers. CONCLUSIONS: PR is associated with changes in oral microbiota. Specifically, PR increases salivary Prevotella melaninogenica and avoids the decline in Rothia and the increase in Streptococcus and Lautropia in responders, which may contribute to the benefits of PR.

Saliva as a non-invasive specimen for COPD assessment.

BACKGROUND: People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. METHODS: Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients' oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. RESULTS: 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. CONCLUSION: Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.