Metagenomics in inflammatory bowel disease.

Abstract

The gut commensal microbiota is known to play a crucial role in maintaining intestinal homeostasis. Alterations in the microbial community composition, also known as dysbiosis, may put health status in risk and increase susceptibility to diseases. Although several diseases have been related to shifts in the gut microbiome composition, it is still uncertain whether those alterations are the cause or consequence of the disease. Inflammatory bowel disease (IBD) is a chronic inflammatory disease with periods of active and inactive inflammation that constitutes to an important health problem. It is divided in two subtypes: Crohn’s disease (CD) and ulcerative colitis (UC) that present similar symptoms but different clinical manifestations. IBD has been widely associated with an alteration of the gut microbiome composition. Nevertheless, there is no clear consensus on the microbial pattern characteristic of the disorders. Main discordances between studies are related to differences between UC and CD. Some previous publications indicate that UC microbial composition is very similar to healthy and differs from CD whereas others consider both subtypes as a unique entity and find high alterations in UC and CD microbial composition in comparison with the microbiome of healthy individuals. The aim of this thesis was to characterize the dysbiosis in a Spanish IBD cohort to evaluate to which extend the gut microbiome composition and function could be differentiated between CD and UC and whether microbiome data could be used as diagnostic and prognostic tools. For this purpose, we analyzed fecal samples of healthy individuals, CD (affected in the ileum) and UC patients using two different methodologies: 16S rRNA gene (or 16S rDNA) and shotgun (short genomic fragments) sequencing. As expected, we observed the presence of dysbiosis in IBD. Furthermore, we showed that microbial composition and function alterations were different for CD and UC, with greater dysbiosis in CD than in UC and with UC resembling more to a healthy state. Functional findings also confirmed this higher dysbiosis in CD than in UC and revealed genes implicated in metabolism pathways and in immune diseases in higher abundance in CD compared with healthy individuals and UC. Although 16S rDNA and shotgun data did not detect differences in the dysbiosis in CD and UC in a consistent manner, both methodologies allowed the classification of IBD subtypes in a similar proportion. Future studies should validate these results using other patient cohorts such as colonic CD or recently diagnosed patients before the application of these techniques as diagnostic tools in clinical practice.

Date of Award	8 Nov 2019
Original language	English
Supervisor	Chaysavanh Manichanh (Director) & Victor Manuel Vargas Blasco (Tutor)