Composition Of Gut Virome Research Articles

A nested case-control study on the association of gut virome in early pregnancy and gestational diabetes mellitus.

Recent studies have increasingly shown the connection between gut microbiome and gestational diabetes mellitus (GDM). However, no studies have explored the relationship between the gut virome and GDM, and the underlying mechanism remains unknown. We performed a nested case-control study within a follow-up cohort, enrolling 51 patients with GDM and 51 healthy controls. Shotgun metagenomics sequencing was used to explore gut virome profiles during early pregnancy. Diversity analysis revealed no difference in the overall gut virome composition between two groups, however, we found greater abundance of Escherichia phage SH2026Stx1 (Q = 0.23), Enterobacteria phage mEp043 c-1 (Q = 0.21), crAssphage cr50_1 (Q = 0.21), Enterobacteria phage phi80 (Q = 0.21), and Escherichia phage HK106 (Q = 0.23) in GDM patients. Cross-kingdom correlation analysis showed the negative correlation between the gut bacterium Eubacterium eligens and three bacteriophages (Escherichia phage SH2026Stx1, Enterobacteria phage mEp043 c-1, and Escherichia phage HK106) in GDM group (r < 0, P < 0.05). Based on gut microbial features and clinical indicators, we constructed a new prediction model using random forest method for GDM with good predictive performance (AUC of 0.893, 95% CI: 0.736 ∼ 0.990). This study is the first to investigate the relationship between the gut virome and GDM as well as the cross-kingdom correlation between gut viruses and bacteria in GDM. Our findings could enhance strategies for preventing and treating GDM from the perspective of gut microbiome, offering valuable insights into its pathogenesis.

Does the Human Gut Virome Contribute to Host Health or Disease?

The human gastrointestinal (GI) tract harbors eukaryotic and prokaryotic viruses and their genomes, metabolites, and proteins, collectively known as the "gut virome". This complex community of viruses colonizing the enteric mucosa is pivotal in regulating host immunity. The mechanisms involved in cross communication between mucosal immunity and the gut virome, as well as their relationship in health and disease, remain largely unknown. Herein, we review the literature on the human gut virome's composition and evolution and the interplay between the gut virome and enteric mucosal immunity and their molecular mechanisms. Our review suggests that future research efforts should focus on unraveling the mechanisms of gut viruses in human homeostasis and pathophysiology and on developing virus-prompted precision therapies.

Community Types of the Human Gut Virome are Associated with Endoscopic Outcome in Ulcerative Colitis.

Inflammatory bowel disease [IBD] is a major debilitating disease. Recently, the gut microbiota has gained attention as an important factor involved in the pathophysiology of IBD. As a complement to the established bacterial 'enterotypes' associated with IBD, we focused here on viruses. We investigated the intestinal virome of IBD patients undergoing biological therapy for the presence of virome configurations associated with IBD, and to uncover how those configurations are associated with therapeutic success. Viral-like particle enrichment followed by deep sequencing was performed on 432 faecal samples from 181 IBD patients starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into 'viral community types', respectively. Patients were stratified based on unsupervised clustering into two viral community types. Community type CA showed a low α-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated with the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Crassvirales and Malgrandaviricetes phages. During post-interventional analysis, endoscopic outcome was associated with gut virome composition. Remitting UC patients had a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Pre-interventional analyses also identified five novel phages associated with treatment success. This study proposed two gut virome configurations that may be involved in the pathophysiology of IBD. Interestingly, those viral configurations are further associated with therapeutic success, suggesting a potential clinical relevance.

DOP53 Community types of the human gut virome are associated with endoscopic outcome in UC patients

Abstract Background Inflammatory bowel diseases (IBD) are a group of chronic inflammatory diseases of the gut. The pathophysiology is unknown; however, it is thought to result from an inappropriate immune reaction to the commensal gut microbiota. Community-typing is a common practice in bacteriome analysis allowing for the stratification of individuals based on their gut microbiome (eg., ‘enterotyping’). A viral counterpart of these enterotypes might allow stratification of individuals based on their gut virome. The aim of the present study is to investigate the existence of such viral community types and assess the impact of therapeutic outcome (and other covariates) on the gut virome in IBD patients. Methods Fecal samples were selected from 181 patients undergoing immunomodulatory therapy, and a baseline (pre-intervention) and a primary endpoint (post-intervention) have been collected for each patient. Viral metagenomics and deep sequencing were performed following viral enrichment with the NetoVIR protocol. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into viral community types, respectively. Results IBD patients were stratified based on unsupervised machine learning into two viral community types. Community type CA showed a low α-diversity and a high relative abundance of Caudoviricetes [non-CrAss] phages and was associated to the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Caudoviricetes [CrAss] and Malgrandaviricetes phages. The gut virome variation was explained by several factors: patients’ individuality (75.8%), disease location (1.4%), age (0.5%) and faecal moisture (0.3%), with diagnosis not showing a non-redundant effect. Despite our expectations the choice of biological therapy did not show an association with the virome variation. During post-interventional analysis, endoscopic outcome (0.5%) was associated to gut virome variation as well. Remitting UC, but not CD, patients revealed a high percentage of community type CrM, a high Shannon diversity and a low phage lysogenic potential. Conversely, non-remitting UC, but not CD, patients revealed a high percentage of community type CA, a low Shannon diversity and a high lysogenic potential. Conclusion These findings suggest that viral community-typing allows for stratification of IBD patients based on their gut virome composition and might be a valuable tool to better understand IBD subtypes or as a potential future biomarker.

Alterations of the gut virome in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that has been linked to the dysbiosis of the gut microbiome and virome. However, the potential characterization of the gut virome in SLE patients needs to be explored more extensively. Herein, we analyzed the gut viral community of 16 SLE patients and 31 healthy controls using both bulk and virus-like particle (VLP)-based metagenomic sequencing of their fecal samples. A total of 15,999 non-redundant viral operational taxonomic units (vOTUs) were identified from the metagenomic assembled contigs and used for gut virome profiling. SLE patients exhibited a significant decrease in gut viral diversity in the bulk metagenome dataset, but this change was not significant in the VLP metagenome dataset. Also, considerable alterations of the overall gut virome composition and remarkable changes in the viral family compositions were observed in SLE patients compared with healthy controls, as observed in both two technologies. We identified 408 vOTUs (177 SLE-enriched and 231 control-enriched) with significantly different relative abundances between patients and controls in the bulk virome, and 18 vOTUs (17 SLE-enriched in 1 control-enriched) in the VLP virome. The SLE-enriched vOTUs included numerous Siphoviridae, Microviridae, and crAss-like viruses and were frequently predicted to infect Bacteroides, Parabacteroides, and Ruminococcus_E, while the control-enriched contained numerous members of Siphoviridae and Myoviridae and were predicted to infect Prevotella and Lachnospirales_CAG-274. We explored the correlations between gut viruses and bacteria and found that some Lachnospirales_CAG-274 and Hungatella_A phages may play key roles in the virus-bacterium network. Furthermore, we explored the gut viral signatures for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of above 0.95, suggesting the potential of the gut virome in the prediction of SLE. Our findings demonstrated the alterations in viral diversity and taxonomic composition of the gut virome of SLE patients. Further research into the etiology of SLE and the gut viral community will open up new avenues for treating and preventing SLE and other autoimmune diseases.

Impact of HIV infection and integrase strand transfer inhibitors-based treatment on the gut virome

Viruses are the most abundant components of the human gut microbiome with a significant impact on health and disease. The effects of human immunodeficiency virus (HIV) infection on gut virome has been scarcely analysed. Several studies suggested that integrase strand transfers inhibitors (INSTIs) are associated with a healthier gut. Thus, the objective of this work was to evaluate the effects of HIV infection and INSTIs on gut virome composition. 26 non-HIV-infected volunteers, 15 naive HIV-infected patients and 15 INSTIs-treated HIV-infected patients were recruited and their gut virome composition was analysed using shotgun sequencing. Bacteriophages were the most abundant and diverse viruses present in gut. HIV infection was accompanied by a decrease in phage richness which was reverted after INSTIs-based treatment. β-diversity of phages revealed that samples from HIV-infected patients clustered separately from those belonging to the control group. Differential abundant analysis showed an increase in phages belonging to Caudoviricetes class in the naive group and a decrease of Malgrandaviricetes class phages in the INSTIs-treated group compared to the control group. Besides, it was observed that INSTIs-based treatment was not able to reverse the increase of lysogenic phages associated with HIV infection or to modify the decrease observed on the relative abundance of Proteobacteria-infecting phages. Our study describes for the first time the impact of HIV and INSTIs on gut virome and demonstrates that INSTIs-based treatments are able to partially restore gut dysbiosis at the viral level, which opens several opportunities for new studies focused on microbiota-based therapies.

The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites

BackgroundThe gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition.MethodsHere, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS.ResultsA majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome.ConclusionOur results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction.

DOP016 Metagenomic analysis of intestinal mucosa revealed an IBD-specific shift in the eukaryotic gut virome composition at early stages of gut inflammation

DOP016 Metagenomic analysis of intestinal mucosa revealed an IBD-specific shift in the eukaryotic gut virome composition at early stages of gut inflammation

Beyond the gut bacterial microbiota: The gut virome.

The gastrointestinal tract is colonized with a highly different population of bacterial, viral, ad fungal species; viruses are reported to be dominant. The composition of gut virome is closely related to dietary habits and surrounding environment. Host and their intestinal microbes live in a dynamic equilibrium and viruses stimulate a low degree of immune responses without causing symptoms (host tolerance). However, intestinal phages could lead to a rupture of eubiosis and may contribute to the shift from health to disease in humans and animals. Viral nucleic acids and other products of lysis of bacteria serve as pathogen‐associated molecular patterns (PAMPs) and could trigger specific inflammatory modulations. At the same time, phages could elicit innate antiviral immune responses. Toll‐like receptors (TLRs) operated as innate antiviral immune sensors and their activation triggers signaling cascades that lead to inflammatory response. J. Med. Virol. 88:1467–1472, 2016. © 2016 Wiley Periodicals, Inc.