Gut microbiome investigation in celiac disease: from methods to its pathogenetic role

Our body is inhabited by a variety of microbes (microbiota), mainly bacteria, that outnumber our own cells. Until recently, most of what we knew about the human microbiota was based on culture methods, whereas a large part of the microbiota is uncultivable, and consequently previous information was limited. The advent of culture-independent methods and, particularly, of next-generation sequencing (NGS) methodology, marked a turning point in studies of the microbiota in terms of its composition and of the genes encoded by these microbes (microbiome). The microbiome is influenced predominantly by environmental factors that cause a large inter-individual variability (~20%) being its heritability only 1.9%. The gut microbiome plays a relevant role in human physiology, and its alteration ("dysbiosis") has been linked to a variety of inflammatory gut diseases, including celiac disease (CD). CD is a chronic, immune-mediated disorder that is triggered by both genetic (mainly HLA-DQ2/DQ8 haplotypes) and environmental factors (gluten), but, in recent years, a large body of experimental evidence suggested that the gut microbiome is an additional contributing factor to the pathogenesis of CD. In this review, we summarize the literature that has investigated the gut microbiome associated with CD, the methods and biological samples usually employed in CD microbiome investigations and the putative pathogenetic role of specific microbial alterations in CD. In conclusion, both gluten-microbe and host-microbe interactions drive the gluten-mediated immune response. However, it remains to be established whether the CD-associated dysbiosis is the consequence of the disease, a simple concomitant association or a concurring causative factor