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

Abstract

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 alpha-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 alpha-diversity and a high relative abundance of Caudoviricetes [CrAss] and Malgrandaviricetes phages. Gut virome variation was explained by patient 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.

Competing Interest Statement

Severine Vermeire has received grants from AbbVie, J&J, Pfizer, Galapagos, Takeda. SV has received consulting and/or speaking fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, Zealand Pharma. Other authors report no conflict of interest.

Funding Statement

This research was supported by the Fonds Wetenschappelijk Onderzoek (Research foundation Flanders) (Daan Jansen: 1S78021N, Kathleen Machiels: 12M9118N)

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by the ethical commission of UZ Leuven (KU Leuven, reference number: S53684). Participants provided signed informed consent to participate with the study. The design of the study was in accordance with the Declaration of Helsinki and Belgian privacy law.

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Data Availability

All data produced in the present work are contained in the manuscript

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