Probiotics to Prevent Celiac Disease and Inflammatory Bowel Diseases.

The incidence of chronic inflammatory diseases (CIDs) is dramatically increasing in the developed world, resulting in an increased burden of disease in childhood. Currently, there are limited effective strategies for treating or preventing these conditions. To date, myriads of cross-sectional studies have described alterations in the composition of the gut microbiota in a variety of disease states, after the disease has already occurred. We suggest that to mechanically link these microbiome changes with disease pathogenesis, a prospective cohort design is needed to capture changes that precede or coincide with disease onset and symptoms. In addition, these prospective studies must integrate microbiological, metagenomic, meta transcriptomic and metabolomic data with minimal and standardized clinical and environmental metadata that allow to correctly compare and interpret the results of the analysis of the human microbiota in order to build a system-level model of the interactions between the host and the development of the disease. The creation of new biological computational models thus constructed will allow us to finally move from the detection of simple elements of "association" to the identification of elements of real "causality" allowing to provide a mechanistic approach to the exploration of the development of CIDs.This can only be done when these diseases are studied as complex biological networks. In this chapter we discuss the current knowledge regarding the contribution of the microbiome to CID in childhood, focusing on celiac disease and inflammatory bowel disease, with the overall aim of identifying pathways to shift research from descriptive to mechanistic approaches. We then examine how some components of the microbiota, through epigenetic reprogramming, can start the march from genetic predisposition to clinical expression of CIDs, thus opening up new possibilities for intervention, through microbiota therapy targeting the manipulation of the composition and function of the microbiota, for future applications of precision medicine and primary prevention.