Gut mucosal virome alterations in ulcerative colitis
Authors: Whitney Tang
Paul K S Chan
Fen Zhang
Joseph J Y Sung
Xiao-Juan Lu
Risheng Zhao
Jun Yu
Chun Pan Cheung
Qian Cao
Siew C Ng
Siu Lam
Francis K L Chan
Jian-Qiu Sheng
Jessica Y L Ching
Yu Zhang
Tao Zuo
Journal: Gut (2019)
Discipline: CLINICAL MEDICINE
Keywords: bacteria; gut mucosa; ulcerative colitis; virome; virome metacommunity.
Affiliations: Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China., State Key Laboratory for digestive disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China., Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese Univetsity of Hong Kong, Shatin, Hong Kong, China., Department of Gastroenterology, The General Hospital of the People's Liberation Army, Beijing, China., Faculty of Medicine, Zhejiang University, Hangzhou, China., Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China., Department of Gastroenterology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 The authors report as highest abundant phage the phiX phage 174 of E. coli. While this can be of biological origin, this phage is also used as positive control during various sequencing procedures and is likely not of biological origin. The authors did not include any negative control, and therefore likely contaminants appear in the results. This is based that a large amount of phages do not have hosts in animals, like the phages of plant associated bacteria (Bradyrhizobium, Ralstonia, Xanthomonas), non-animal associated amoeba (Mimivirus, Megavirus) and environmental bacteria (Yellowstone lake phage; Caulobacter; Brevibacillus; Salinibacter; Prochlorococcus). Issues can further be seen in the authors bacterial sequencing data, which does not show the usual Firmicutes Bacteroidetes split, which is expected in the gut, but rather shows other possible contaminants like Massilia, which is mostly (but not exclusively) an environmental bacterium, Pseudomonas (not usually seen in the gut, but a common contaminant) and Cryocola (an antarctic bacterium), and these already form more than 50% of their data. ,