Community types of the human gut virome are associated with endoscopic outcome in ulcerative colitis
Authors: Jansen Daan , Falony Gwen , Vieira-Silva Sara , Simsek Ceren , Marcelis Tine , Caenepeel Clara , Machiels Kathleen , Raes Jeroen , Vermeire Séverine , Matthijnssens Jelle 
Published: July 2022

Objective

IBD patients have an altered gut virome composition; however, the relationship to disease is unknown. Our aim is to investigate the existence of viral community types and assess the impact of therapeutic outcome (and other covariates) on the gut virome.

Design

Viral particle enrichment followed by deep sequencing (1.52 TB) was performed on 432 faecal samples from 181 IBD patients (CD=126;UC=55) starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures determined covariates of the virome composition and condensed the gut virota into viral community types.

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. Gut virome variation was explained by patients’ individuality (75.8%), disease location (1.4%), age (0.5%) and faecal moisture (0.3%), with diagnosis not showing a non-redundant effect. Endoscopic outcome (0.5%) was accompanied by gut virome shifts in UC. Non-remitting UC, but not CD, patients revealed a high percentage of community type CA, a low diversity, and a high lysogenic potential. During pre-interventional analysis, we discovered five novel phages with a predictive value for therapeutic outcome.

Conclusion

The gut virota shows the existence of distinct virome configurations that are associated with endoscopic outcome, and community typing could be a valuable tool to improve our understanding about IBD subtypes, pathology, and activity.

Significance of this study

What is already known on this subject?

Bacterial community typing (‘enterotyping’) is an established practice to stratify individuals based on their bacteriome composition

IBD pathology is repeatedly associated with alterations in the gut virome reflected by a high Caudovirales and low Microviridae abundance

IBD pathology is associated with a shift in phage lifestyle towards a highly lysogenic state of the gut virome

What are the new findings?

Viral community types exist and could stratify individuals based on their gut virome composition in a large prospective multi-therapeutic IBD cohort

Viral community types could be associated to the dysbiotic Bact2-enterotype

Endoscopic outcome (remission/non-remission) was a significant covariate of the gut virome composition post-intervention and could be associated with viral community types in UC patients

Non-remitting UC patients revealed a low diversity and a high abundance of lysogenic phages

We discovered five novel phages (e.g., novel CrAss-like phage) associated with predicting treatment success

How might it impact the clinical practice in the foreseeable future?

Viral community types could be a valuable tool to investigate IBD pathology and to differentiate between IBD subtypes and disease activity

Viral community typing might distinguish a healthy gut from a dysbiotic gut virome

Clinical studies should validate phages as predictive biomarkers in IBD patients starting therapy