Inflammatory bowel disease (IBD)
Crohn’s disease (CD) and ulcerative colitis (UC), the 2 major forms of IBD, show a strong genetic component, and we have contributed recent breakthrough discoveries within the frame of large international consortia. While 163 IBD risk loci have been already discovered, our current challenge is to exploit this information for the identification of novel diagnostic and/or therapeutic targets, and for the delineation of genotype-based strategies to personalized medicine. We have also undertaken the functional characterization of IBD risk genes of unknown pathogenetic role.We are partners of large multi-national consortia, including the International IBD Genetics Consortium (IIBDGC; www.ibdgenetics.org) and the EU project IBD-Character (www.ibdcharacter.eu).
Irritable bowel syndrome (IBS)
A heritable component of IBS is recognized, though no unequivocal IBS risk genes have been yet identified. One important exception may be TNFSF15, which we first described in IBS and has now been confirmed in independent studies. We believe the current IBS “label” is inadequate to capture the true spectrum of similar disorders, where the weight of genetic factors in the determination of disease risk can be considerably different, ranging from rare single-gene forms to extremely complex polygenic conditions. We aim to unravel key IBS pathogenetic mechanisms by combining genome-wide association studies (GWAS) of common risk variants in the general population, targeted and whole-exome sequencing for the identification of rare variants in subsets of IBS patients, and functional characterization of risk genes and associated causative alleles. We have established an extensive network of collaboration with other centers around the world, and coordinate the bellygenes initiative (www.bellygenes.org).
Other GI conditions
Similar to IBS, a genetic component has been reported also for gastroesophageal reflux disease (GERD), microscopic colitis, diverticulitis and other GI diseases. We are running initial GWAS and targeted analyses, with the overarching goal to fill the knowledge gap and gain increased pathogenetic understanding. For these studies as well, we have established an international network of collaboration.
Genes, microbiota and gut function
Variation in the composition of gut microbiota is of relevance to human diseases but still poorly understood are the factors that induce and/or maintain such variation. We study this interaction to understand whether, and if so how, the genetic make-up of the host affects the composition of the human microbiota, and approach this question through computational assessment of host genome vs microbiome comparisons. We are also interested in the potential to correlate microbiota variation with human bowel behavior and function, particularly in relation to endophenotypes of IBS (colonic transit, stool frequency etc). Finally, we aim to establish computational models to describe and predict how these three elements (host genome, gut microbiome and gut function) are functionally and causally related in gastrointestinal health and disease.