Community types of the human gut virome are associated with endoscopic outcome in ulcerative colitis

Abstract Background Inflammatory Bowel Diseases (IBD) are a group of chronic inflammatory diseases of the gut. IBD patients have an altered gut microbiota; however, the relationship to disease is unknown. The gut microbiota is a complex ecosystem and bacterial community-typing is an established approach to condense the microbial complexity into enterotypes. A viral counterpart of enterotypes might allow stratification of individuals based on their gut virome. We aim to investigate the existence of such viral community types and assess the impact of therapeutic outcome (and other covariates) on the gut virome in IBD patients. Methods Viral particle enrichment followed by deep sequencing (1.52TB) was performed on 432 faecal samples from 181 IBD patients (CD = 126;UC = 55) starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into viral community types, respectively. Results IBD patients were stratified based on unsupervised machine learning into two viral community types. Community type CA showed a low α-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated to the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Caudoviricetes [CrAss] and Malgrandaviricetes phages. The gut virome variation was explained by several factors: patient individuality (75.8%), disease location (1.4%), age (0.5%) and faecal moisture (0.3%), whereas diagnosis did not show a non-redundant effect. Despite our expectations the choice of biological therapy did not show an association with the virome variation. During post-interventional analysis, endoscopic outcome (0.5%) was associated to gut virome variation. Remitting UC, but not CD, patients revealed a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Conversely, non-remitting UC, but not CD, patients revealed a high percentage of community type CA, a low Shannon diversity and a high lysogenic potential. During pre-interventional analysis, we discovered five novel phages associated with treatment success. Conclusion The gut virota shows the existence of distinct virome configurations that are associated with endoscopic outcome. Therefore, community typing could be a valuable tool to improve our understanding about IBD subtypes, pathology, and activity.