Gut mucosal virome alterations in ulcerative colitis

Zuo, Tao; Lu, Xiaobo; Zhang, Yu; Cheung, Chun Pan; Lam, Sylvia; Zhang, Fen; Tang, Whitney; Ching, Jessica Y. L.; Zhao, Risheng; Chan, Paul K.S.; Sung, Joseph J.Y.; Yu, Jun; Chan, Francis K.L.; Cao, Qian; Sheng, Jian-qiu; Ng, Siew C.

doi:10.1136/gutjnl-2018-318131

Cited by 320 publications

(322 citation statements)

References 53 publications

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“…The total collection of vaginal viruses (the vaginal “virome”), has only been sparsely investigated, but there is increasing evidence that bacteriophages (or “phages”) are a factor in certain diseases related to gut microbiome dysbiosis[9]. Further, phages adhere to and are significantly enriched in mucosal surfaces, possibly providing what has been termed “non-host derived immunity” against infection[10,11].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility

Jakobsen

Haahr

Humaıdan

et al. 2019

Preprint

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18Background. Bacterial vaginosis (BV) is characterised by a reduction in Lactobacillus spp. abundance and 19 increased abundance of facultative anaerobes, like Gardnerella vaginalis. BV aetiology is not fully 20 understood, but bacteriophages could play a pivotal role causing perturbation of the vaginal bacterial 21 community. Here we investigate the vaginal viral community, including bacteriophages, and its association 22 to the bacterial community and BV-status. 23 Methods. Vaginal samples from 48 patients undergoing IVF treatment for non-female factor infertility were 24 subjected to metagenomic sequencing of purified virus-like particles. The vaginal viral community was 25 characterized and correlated with BV-status, bacterial community structure and presence of key vaginal 26 bacterial species. 27 Results. The majority of identified vaginal viruses belonged to the class of double-stranded DNA 28 bacteriophages, with eukaryotic viruses constituting 4% of total reads. Clear links between viral community 29 composition and BV (q = 0.006, R = 0.26) as well as presence of L. crispatus (q = 0.001, R = 0.43), L. iners, 30 Gardnerella vaginalis and Atopobium vaginae were found (q < 0.002, R > 0.15). Interestingly, also the 31 eukaryotic viral community was correlated with BV-status (q = 0.018, R = 0.20). 32 Conclusions. The vaginal virome is clearly linked with bacterial community structure and BV-status. 33 Clinical Trials Registration. NCT02042352. 34 Word count abstract: 200 36 Word count main text: 3467 37

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Section: Introductionmentioning

confidence: 99%

Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility

Jakobsen

Haahr

Humaıdan

et al. 2019

Preprint

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“…Immune-related digestive system inflammation, including colitis, hepatitis, pancreatitis, can be caused by a variety of pathogenic factors, such as genetic abnormality, autoimmune factors, immune-related drugs, viral infections, and so on (1)(2)(3)(4). PD-L1(B7-H1) is thought to be involved in the regulation of cellular and humoral immune responses through the PD-1 receptor on activated T and B cells (5,6).…”

Section: Introductionmentioning

confidence: 99%

The Risk Ratio of Immune-Related Colitis, Hepatitis, and Pancreatitis in Patients With Solid Tumors Caused by PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

et al. 2020

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Purpose: The meta-analysis was put into practice in evaluating the risk ratio of immune-related digestive system inflammation in patients with solid tumors caused by PD-1/PD-L1 inhibitors.Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Results: After screening and eligibility assessment, a total of 26 clinical trials involving 16,409 patients were selected for the final quantitative synthesis. Immune-related digestive system inflammations, including colitis, hepatitis, pancreatitis, were evaluated separately. Compared with chemotherapy, PD-1/PD-L1 inhibitors led to an increase in the incidence risk of all grade colitis (RR = 2.43, 95% CI: [1.23, 4.82], P = 0.01). Similar incidence trend could also be seen when PD-1/PD-L1 inhibitors were combined with chemotherapy (RR = 2.62, 95% CI: [1.25, 5.48], P = 0.01). Whether compared with Nivolumab plus Ipilimumab or Ipilimumab alone, the incidence risk of colitis in the Nivolumab group was significantly lower than that of the control group. Similar analysis results could also be seen in the incidence risk of hepatitis. We did not find a statistically significant effect on the incidence of immune-related pancreatitis after the use of PD-1/PD-L1 inhibitors.Tian et al.Inflammation and Anti-PD-1/PD-L1 Therapy Conclusion: The use of PD-1/PD-L1 inhibitors increased the incidence risk of immune-related colitis and hepatitis, but this potential to increase the incidence risk of the disease was weaker than Ipilimumab.

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“…For example, there have been more attempts to characterize “healthy gut phageome” since a study in 2016 conducted deep-sequencing of DNA from virus-like particles (VLP) and revealed the presence of completely assembled phage genomes in 64 healthy individuals around the world (8). Attempts have also been made to explore the associations between human gut virome alterations and diseases (7, 9, 10). However, only a small number of metagenomic studies focused on oral phage communities (5), including a study in 2014 that reported an alteration of virome composition in subjects with periodontal disease (11).…”

Section: Introductionmentioning

confidence: 99%

Long-read shotgun metagenome sequencing using PromethION uncovers novel bacteriophages, their abundance, and interaction with host bacterial immunity in the oral microbiota

Yahara

Suzuki

Hirabayashi

et al. 2020

Preprint

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17 18 Bacteriophages (phages), or bacterial viruses, are very diverse and highly abundant worldwide, 19 including human microbiomes. Although a few metagenomic studies have focused on oral 20 phages, they relied on short-read sequencing. Here, we conducted a long-read metagenomic 21 study of human saliva for the first time using PromethION that requires a smaller amount of 22 DNA than PacBio. Our analyses, which integrated both PromethION and HiSeq data of >30 Gb 23 per sample, revealed N50 ranging from 187-345 kb and thousands of contigs with >1 kb 24 accounting for > 99% of all contigs on which 94-96% of HiSeq reads were mapped. We 25 identified hundreds of viral contigs (95 phages and 333 prophages on an average per sample); 26 0-43.8% and 12.5-56.3% of the "most confident" phages and prophages, respectively, didn't 27 cluster with those reported previously and were identified as novel. Our integrated analyses 28 identified highly abundant oral phages/prophages, including a novel Streptococcus phage 29 cluster and nine jumbo phages/prophages. Interestingly, 86% of the phage cluster and 67% of 30 the jumbo phages/prophages contained remote homologs of antimicrobial resistance genes, 31 suggesting their potential role as a source of recombination to generate new resistance genes. 32Pan-genome analysis of the phages/prophages revealed remarkable diversity, identifying 0.3% 33 and 86.4% of the genes as core and singletons, respectively. Functional annotation revealed 34 that the highest fraction of the core genes was enriched in phage morphogenesis, followed by 35 the fraction enriched in host cellular processes. Furthermore, our study suggested that oral 36 phages present in human saliva are under selective pressure for escaping CRISPR immunity. 37 (250/250 words) 38 39 Importance 40 41Despite the abundance and grave implications oral bacterial viruses in health and disease, little 42 is known regarding the different groups of oral bacterial viruses, their relative abundances 43 under various conditions, and their activities. We provided answers to these questions for the first time utilizing a recently developed sequencer that can capture and sequence long DNA 45 fragments, including viruses, and requires only a small amount of DNA input, making it 46 suitable for analyzing human oral samples. We identified hundreds of viral sequences, 47 (147/150 words) 54 55

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Gut mucosal virome alterations in ulcerative colitis

Cited by 320 publications

References 53 publications

Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility

Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility

The Risk Ratio of Immune-Related Colitis, Hepatitis, and Pancreatitis in Patients With Solid Tumors Caused by PD-1/PD-L1 Inhibitors: A Systematic Review and Meta-Analysis

Long-read shotgun metagenome sequencing using PromethION uncovers novel bacteriophages, their abundance, and interaction with host bacterial immunity in the oral microbiota

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