Maturation of microbial networks across body sites is associated with susceptibility to childhood respiratory infections

Introduction: Respiratory and gut microbiota compositions have been associated with susceptibility to and severity of respiratory tract infections (RTI). Microbial communities within specific sites are known to communicate with one another, thereby forming cross-niche networks typifying the overarching human microbiome and its function. Aim: We assessed the maturation of cross-niche microbial networks early in life and their association with susceptibility to RTIs in children. Methods: We applied network analysis (spiecEasi), indicator species analysis and community clustering to generate microbial networks across body sites using 16S rRNA sequence data from oral, nasopharyngeal and fecal samples of 120 healthy infants at 1 week, 2, 4 and 6 months of life. Networks were stratified based on the number of RTIs a child experienced over the first year of life. Results: At 1 week, microbial networks from infants experiencing 0-2 RTIs were already well defined by four large clusters: three clusters composed of niche-specific species and one connecting cluster composed of mixed species. These clusters were stable over time regarding composition, size and connectivity. More susceptible infants showed fragmented microbial networks that were composed of small, less connected clusters, suggesting decreased microbial topography across sites. Discussion: Our results highlight the existence of a cross-niche microbial network within the infant microbiome that is associated with susceptibility to RTIs in the first year of life. This may lead to new insights for preventing RTIs in childhood and help to understand the role of early life microbiome maturation in health and disease.