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Giske Biesbroek

Thursday 22 May 2014

Dynamics and drivers of the respiratory microbiome in healthy children

Promotor: Prof. dr E.A.M. Sanders
Defence: 22 May 2014

Respiratory tract infections are a major cause of mortality and morbidity worldwide and affects mostly the very young. Although carriage of potential pathogens (pathobionts) in the respiratory tract is an important prerequisite for infection, it remains unclear what mechanisms define if carriers progress towards disease. By the availability of innovative sequencing techniques we now know we are colonized not only by pathobionts, but by in total more than 1 trillion bacteria, the microbiome. These bacteria have a beneficial function to us: they mature our immune system and mucosal barriers and help resist colonization by pathogens. Subsequently, changes in bacterial community characteristics, like types or relative amounts of bacteria present and changes in their functional ability are increasingly associated with diseases. Since the microbiome might play a role in the etiology of respiratory infections as well, we aimed to obtain a better understanding of bacterial community characteristics in healthy young children to ultimately provide a foundation for future research that focuses on pathophysiological processes in respiratory disease. We characterized the microbiota in approx. 800 nasopharyngeal samples obtained from healthy children who had participated in a randomized controlled trail that studied efficacy of reduced-dose schedules of pneumococcal conjugate vaccination (PCV-7) on carriage of Streptococcus pneumoniae in the Netherlands.
The major conclusions of this thesis are that 1) early microbiome profiles in the upper respiratory tract exist and that they are associated to stability or patterns of change in the first two years of life. 2) In line with studies performed on the intestinal microbiome, we observed that breastfeeding plays an important role in colonization patterns in early life by enhancement of the non-pathogenic residents. 3) Through identification of specific bacterial–bacterial and viral–bacterial associations we were able to identify key-players in microbiome dynamics. 4) PCV-7 has a major impact on respiratory carriage of the targeted pneumococcal serotypes, but also on a wide variety of bacteria including pathobionts, like Staphylococcus aureus and Haemophilus influenza, and commensals. Possibly elimination of a common bacterial colonizer disrupts temporary the highly interactive network of the microbiome. Aformentioned findings are important for understanding the development and structure of the respiratory microbiome in the first years of life. They also provide clues for healthy or susceptible conditions for respiratory tract infection. Herewith, our results can lead to alternative diagnostic, therapeutic and preventive surveillance strategies in respiratory infections. Better understanding of the etiology and individual susceptibility to respiratory tract infections is essential for entangling this major health problem in children.