PT  - JOURNAL ARTICLE
AU  - Tao Zuo
AU  - Xiao-Juan Lu
AU  - Yu Zhang
AU  - Chun Pan Cheung
AU  - Siu Lam
AU  - Fen Zhang
AU  - Whitney Tang
AU  - Jessica Y L Ching
AU  - Risheng Zhao
AU  - Paul K S Chan
AU  - Joseph J Y Sung
AU  - Jun Yu
AU  - Francis K L Chan
AU  - Qian Cao
AU  - Jian-Qiu Sheng
AU  - Siew C Ng
TI  - Gut mucosal virome alterations in ulcerative colitis
AID  - 10.1136/gutjnl-2018-318131
DP  - 2019 Jul 01
TA  - Gut
PG  - 1169--1179
VI  - 68
IP  - 7
4099  - http://gut.bmj.com/content/68/7/1169.short
4100  - http://gut.bmj.com/content/68/7/1169.full
SO  - Gut2019 Jul 01; 68
AB  - 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.