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.

miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis.

Mesenchymal Stromal/Stem Cells (MSC) are currently being explored in diverse clinical applications, including regenerative therapies. Their contribution to regeneration of bone fractures is dependent on their capacity to proliferate, undergo osteogenesis and induce angiogenesis. This study aimed to uncover microRNAs capable of concomitantly regulate these mechanisms. Following microRNA array results, we identified miR-195 and miR-497 as downregulated in human primary MSC under osteogenic differentiation. Overexpression of miR-195 or miR-497 in human primary MSC leads to a decrease in osteogenic differentiation and proliferation rate. Conversely, inhibition of miR-195 increased alkaline phosphatase expression and activity and cells proliferation. Then, miR-195 was used to study MSC capacity to recruit blood vessels in vivo. We provide evidence that the paracrine effect of MSC on angiogenesis is diminishedwhen cells over-express miR-195. VEGF may partially mediate this effect, as its expression and secreted protein levels are reduced by miR-195, while increased by anti-miR-195, in human MSC. Luciferase reporter assays revealed a direct interaction between miR-195 and VEGF 3´-UTR in bone cancer cells. In conclusion, our results suggest that miR-195 regulates important mechanisms for bone regeneration, specifically MSC osteogenic differentiation, proliferation and control of angiogenesis; therefore, it is a potential target for clinical bone regenerative therapies.