Host genetic variation and gut microbiome in pediatric diseases

Pediatric health is the foundation for people's lifelong health. The co-evolution of host genetics and the gut microbiome fosters a symbiotic relationship that is important for pediatric growth and the pathogenesis of various diseases. However, a comprehensive overview of the human genetic-gut microbiome axis in pediatric diseases remains unavailable. This review summarizes the human genetic variants that are associated with pediatric diseases, affecting the nervous, respiratory, and immune systems, as well as those linked to preterm birth (PTB), as identified by genome-wide association studies (GWAS). As the gut microbiome plays a crucial role in pediatric health, we have systematically discussed microbial biomarkers associated with the onset and progression of pediatric diseases, with an emphasis on their clinical impact across four key axes: the gut-brain, gut-lung, gut-skin, and gut-immune axes. The GWAS on the gut microbiome revealed numerous genetic variants that intricately regulate its composition. These variants predispose individuals to gut microbiome dysbiosis, potentially initiating or exacerbating pediatric disease manifestations, as discussed below. Moreover, the underrepresentation of populations from low- and middle-income countries in existing microbiome-related data, coupled with technical challenges, limits our understanding of the association between microbiome and health. Finally, we emphasize the promising potential of elucidating and modulating host gene-gut microbiome interactions to offer novel insights for advancing precision pediatric medicine and developing innovative therapeutic strategies.