The Birth of hologenome: how diet, genes and environment shape the bacterial and fungal gut communities in children

Autoimmune and inflammatory diseases are increasing in western populations of industrialized countries with a shift of disease onset to the pediatric populations. Several evidences indicate that diet globalization, processing of food, urbanization and other environmental factors, such as sanitation and antibiotic treatment are involved in modifications of gut microbiota/mycobiota composition. Alteration of gut microbial profiles could induce inflammation and immune responses, and thus promote inflammatory and autoimmune disorders, such as Inflammatory Bowel Disease (IBD) or rheumatic diseases. This PhD project aims at: 1- dissecting the role of diet and environment on gut microbiota of healthy children from rural and urbanized environments; 2- investigating the association of bacterial and fungal microbiome alterations in pediatric patients affected by inflammatory and autoimmune disorders, dramatically increased in the western world; 3-studying the immunomodulatory potential of fungal isolates in health and disease, and their interaction with bacterial gut communities. In particular, in order to understand the impact of diet and urbanization in shaping the gut microbiota, we investigated the microbiome of healthy children populations having different dietary habits and living in a rural African village and in urban areas (a small town and the capital city of Burkina Faso), comparing with that of children living in Italy. These pediatric populations were selected as representative populations in which the incidence of autoimmune and inflammatory diseases is very low, and as representative of the western and industrialized populations respectively. In order to deepen the knowledge of the pathogenesis of IBD at early onset (EO), we evaluated the phenotype and course of EO-IBD (0–5 years) compared with pediatric lateronset disease (6–11 and 12–18 years). Understanding the factors that contribute to early age of onset of IBD could potentially facilitate intervention strategy development. Then, we characterized the gut microbiota composition of children affected by Juvenile Idiopathic Arthritis (JIA), a typical immune-mediated condition that is largely increasing in western pediatric populations in order to define specific microbial "pro-arthritogenic" profiles, in association with HLA-B27 status. Furthermore, we investigated the gut mycobiota composition in the healthy population at different age range, characterizing phenotypically the fungal isolates for traits related to adaptation in the gut environment and for potential pathogenic traits. Finally, we characterized phenotypically and immunologically fungal isolates from pediatric IBD patients in order to understand the potential role of fungal strains in etiology of IBD, and their interaction with microbiota.