Viral metagenomic analysis of fecal samples reveals an enteric virome signature in irritable bowel syndrome

Ansari, Mina; Ebrahimi, Mehregan; Fattahi, Mohammad Reza; Gardner, Michael G.; Safarpour, Ali Reza; Faghihi, Mohammad Ali; Lankarani, Kamran Bagheri

doi:10.1186/s12866-020-01817-4

Cited by 20 publications

(11 citation statements)

References 73 publications

(79 reference statements)

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“…The larger study presented here examines both known and unknown viral sequences. We corroborated the reduction in phage alpha diversity in IBS and lack of robust differentiation among IBS subtypes reported by Ansari et al 25 However, we did not identify significant differences in families of eukaryotic viruses of the order Megavirales between patients with IBS and controls, as reported by Ansari et al 25 with the exception of two VCs assigned to the Mimiviridae family, one of which was more abundant in IBS and one with less abundance but we noted that the protein sequence hits used to classify this family had low support. All other members of the Megavirales order in our data had very low abundances and alignment scores and did not display significantly different abundances between IBS and controls.…”

Section: Discussionsupporting

confidence: 92%

“…To our knowledge, there is a single previous report on the gut virome in IBS 25 which investigated the fecal virome of 25 patients with IBS and 17 controls using the subset of reads that could be classified to known viral families by alignment to the Viral RefSeq database. The larger study presented here examines both known and unknown viral sequences.…”

Section: Discussionmentioning

confidence: 99%

“… 17–20 Despite a key role in the gut microbial ecosystem, the virome is relatively understudied in gastrointestinal diseases in contrast to the bacteriome, although recent reports suggest disturbances of the gut virome in inflammatory bowel disease (IBD) 17 , 21–24 and in one small study of IBS. 25 The aims of the present study were, therefore, to investigate if the gut virome is altered in patients with IBS and to determine if any alterations distinguished the symptom-based clinical subtypes of IBS.…”

Section: Introductionmentioning

confidence: 99%

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The gut virome in Irritable Bowel Syndrome differs from that of controls

et al. 2021

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Irritable Bowel Syndrome (IBS), the most common gastrointestinal disorder, is diagnosed solely on symptoms. Potentially diagnostic alterations in the bacterial component of the gut microbiome (the bacteriome) are associated with IBS, but despite the known role of the virome (particularly bacteriophages), in shaping the gut bacteriome, few studies have investigated the virome in IBS. We performed metagenomic sequencing of fecal Virus-Like Particles (VLPs) from 55 patients with IBS and 51 control individuals. We detected significantly lower alpha diversity of viral clusters comprising both known and novel viruses (viral ‘dark matter’) in IBS and a significant difference in beta diversity compared to controls, but not between IBS symptom subtypes. The three most abundant bacteriophage clusters belonged to the Siphoviridae, Myoviridae , and Podoviridae families (Order Caudovirales ). A core virome (defined as a cluster present in at least 50% of samples) of 5 and 12 viral clusters was identified in IBS and control subjects, respectively. We also identified a subset of viral clusters that showed differential abundance between IBS and controls. The virome did not co-vary significantly with the bacteriome, with IBS clinical subtype, or with Bile Acid Malabsorption status. However, differences in the virome could be related back to the bacteriome as analysis of CRISPR spacers indicated that the virome alterations were at least partially related to the alterations in the bacteriome. We found no evidence for a shift from lytic to lysogenic replication of core viral clusters, a phenomenon reported for the gut virome of patients with Inflammatory Bowel Disease. Collectively, our data show alterations in the virome of patients with IBS, regardless of clinical subtype, which may facilitate development of new microbiome-based therapeutics.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The gut virome in Irritable Bowel Syndrome differs from that of controls

et al. 2021

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“…The detrimental effects of CsCl should be avoided to maintain diversity and integrity as much as possible. Additionally, even though sequencing has introduced a wealth of information regarding phage constituents within the microbiome [ 39 , 40 , 41 , 42 , 43 ], it has become apparent that there is a need to move into research that investigates the activity of said phage populations in relation to health and dysbiosis. As such, it is even more important to retain not only the community structure, but the activity.…”

Section: Discussionmentioning

confidence: 99%

Standard Bacteriophage Purification Procedures Cause Loss in Numbers and Activity

Carroll‐Portillo

Coffman

Varga

et al. 2021

Viruses

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For decades, bacteriophage purification has followed structured protocols focused on generating high concentrations of phage in manageable volumes. As research moves toward understanding complex phage populations, purification needs have shifted to maximize the amount of phage while maintaining diversity and activity. The effects of standard phage purification procedures such as polyethylene glycol (PEG) precipitation and cesium chloride (CsCl) density gradients on both diversity and activity of a phage population are not known. We have examined the effects of PEG precipitation and CsCl density gradients on a number of known phage (M13, T4, and ΦX 174) of varying structure and size, individually and as mixed sample. Measurement of phage numbers and activity throughout the purification process was performed. We demonstrate that these methods, used routinely to generate “pure” phage samples, are in fact detrimental to retention of phage number and activity; even more so in mixed phage samples. As such, minimal amounts of processing are recommended to introduce less bias and maintain more of a phage population.

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“…HIV, HPV, HBV, HCV, EBV and IBS-V are associated with ILD, fibrosis and immunological cancers. [3][4][5][6][7] The coronavirus is also associated with ILD and pulmonary fibrosis, suggesting that this virus may play a role in the higher mortality of patients with cancer. [8][9][10] Statins have multiple pleiotropic effects (eg, suppression of inflammation, reduction of oxidative stress and reduction of T cell activation) that have implications for immunomodulatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort

et al. 2021

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ObjectiveTo determine the effect of statins on risk of cancer in patients with interstitial lung disease (ILD) and pulmonary fibrosis.SettingWe retrospectively enrolled patients with ILD and pulmonary fibrosis and divided them into two cohorts by statin use (statin users (n=10 036) and statin non-users (n=10 036)).ParticipantsWe selected patients with ILD and pulmonary fibrosis (N=53 862) from Taiwan’s National Health Insurance Research Database. Time-dependent Cox models were used to compare risk of cancer of propensity-matched statin users and non-users. Cumulative cancer incidence was analysed through Cox proportional regression. We calculated adjusted HRs (aHRs) and their 95% CIs for cancer after adjusting for sex, age, comorbidities, and use of inhaled corticosteroids, oral steroids and statins.ResultsCompared with statin non-users, the aHRs (95% CIs) for statin users were 0.60 (0.55 to 0.65) for cancer, 0.52 (0.35 to 0.78) for haematological malignancy, 0.52 (0.38 to 0.72) for cancer of the head and neck, 0.73 (0.59 to 0.89) for colorectal cancer, 0.34 (0.26 to 0.43) for liver cancer, 0.39 (0.23 to 0.67) for pancreatic cancer, 0.40 (0.17 to 0.96) for skin cancer, 0.67 (0.52 to 0.87) for breast cancer, 0.27 (0.14 to 0.54) for cervical cancer, 0.37 (0.30 to 0.46) for other immunological cancers, 0.73 (0.54 to 0.98) for bladder/kidney cancer and 0.88 (0.71 to 1.09) for lung cancer.ConclusionStatin use is associated with lower risk of cancer in the ILD and pulmonary fibrosis cohort.

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Viral metagenomic analysis of fecal samples reveals an enteric virome signature in irritable bowel syndrome

Cited by 20 publications

References 73 publications

The gut virome in Irritable Bowel Syndrome differs from that of controls

The gut virome in Irritable Bowel Syndrome differs from that of controls

Standard Bacteriophage Purification Procedures Cause Loss in Numbers and Activity

Time-dependent propensity-matched general population study of the effects of statin use on cancer risk in an interstitial lung disease and pulmonary fibrosis cohort

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