Objective The pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC.
Design Deep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2.
Results In UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC.
Conclusion We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.
- gut mucosa
- virome metacommunity
- ulcerative colitis
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Contributors TZ performed the experiments and metagenomics analysis and drafted the manuscript. XJL, YZ and WT performed study subject inclusion and collection of specimens, helped in virome preparation and analysis. CPC, SL, FZ and RZ collected the clinical samples and data, helped in virus DNA extraction and provided significant intellectual contribution. WT and JYLC managed the clinical practice and clinical database. PC, JJYS, JY, FKLC, QC and JQS provided intellectual contribution and critical comments on the manuscript. SCN designed and supervised the study and revised the manuscript.
Funding PROCORE-France/Hong Kong Joint Research Scheme (F-CUHK402/15); ANR/RGC Joint Research Scheme (A-CUHK402/17); the ENIGMA study supported by Helmsley Charitable Trust; and a seed fund for Gut Microbiome Research provided by the Gut Microbiota Research Center, Faculty of Medicine (The Chinese University of Hong Kong).
Competing interests None declared.
Ethics approval The study was approved by The Joint Chinese University of Hong Kong, New Territories East Cluster Clinical Research Ethics Committee (The Joint CUHK-NTEC CREC, CREC Ref No: 2014.026).
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Not required.
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