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Disease/Model | Subjects | Determination | Main Findings | References |
---|---|---|---|---|
Obesity/humans | 128 obese subjects and 101 lean subjects | Gut virome (GV), bacteriome, and viral–bacterial correlations | -Obese subjects, especially those with type 2 diabetes (T2D), had a lower gut viral richness and diversity than lean controls. -GV may play an important role in the development of obesity and T2D. -Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage, were higher in obese subjects than in lean controls. |
[7] |
Inflammatory Bowel disease (IBD)/humans | 12 household controls, 18 Crohn’s disease patients, and 42 ulcerative colitis patients | Stool samples investigated by virus-like particle enrichment and sequencing as well as bacterial 16S rRNA gene analysis | -Patients with IBD showed a significant increase in Caudovirales bacteriophages in their GV. -Changes in the GV may contribute to intestinal inflammation and bacterial dysbiosis. |
[8] |
Cirrhosis and hepatic encephalopathy/humans | 40 controls and 163 cirrhotic patients | Stool metagenomics for bacteria and phages were analyzed in controls versus cirrhosis, within cirrhotic, hospitalized/not, and pre/post rifaximin | -Bacterial α-/β-diversity worsened from controls through cirrhosis patients. Phage α-diversity was similar in both groups. -No changes in α-/β-diversity of phages or bacteria were seen after postrifaximin treatment in cirrhotic patients. |
[1] |
Obesity and metabolic syndrome/humans | 28 school-aged children (10 with normal weight, 10 obese, and 8 obese + metabolic syndrome) | Characterization of the gut DNA virome using metagenomic sequencing | -Phage richness and diversity of individuals with obese and obese + metabolic syndrome tended to increase with respect to controls. -The abundance of some phages correlated with gut bacterial taxa and with anthropometric and biochemical parameters altered in obese and obese + metabolic syndrome. |
[9] |
Bile acid metabolism/mice | 7 germ-free C57BL/6J mice | Phage-induced repression of a tryptophan-rich sensory protein and repression of bile acid deconjugation | -Phages’ presence in the gut can affect the microbial metabolism of bile acids. -Phague BV01 and other phages from the family Salyersviridae are ubiquitous in the human gut, can infect a broad range of Bacteroides hosts, and affect bile acid metabolism. |
[10] |
Cerebral ischemia/mice | 6 adult C57BL/6J mice | Determination of GV composition by shotgun metagenomics in fecal samples | -Following focal ischemia, the abundances of two viral taxa decreased, and those of five viral taxa increased compared with previous cohorts. -Abundances of Clostridia-like phages and Erysipelatoclostridiaceae-like phages were decreased in the stroke compared with previous cohorts |
[11] |
IBD/humans | 40 fecal samples | Stool samples investigated by bioinformatics viral sequencing and bacterial 16S rRNA gene analysis | -Changes in GV and increased numbers of temperate phage sequences were found in individuals with Crohn’s disease. -Incorporating both bacteriome and GV composition offered better discrimination power between health and disease. |
[3] |
Metabolic syndrome/humans | 196 participants with metabolic syndrome preceding cardiometabolic disease | Bulk whole genome and virus-like particle communities | -GV from metabolic syndrome patients exhibited low richness and diversity. -Viral clusters revealed that Candidatus Heliusviridae, a highly widespread gut phage, was found in >90% of metabolic syndrome patients. |
[12] |
Environmental enteric dysfunction and low growth rate/humans | 94 children without diarrhea or human immunodeficiency virus | Gut bacterial and GV sequencing and analysis | - Three differentially abundant phages were identified in GV, depending on child growth velocities. -A positive correlation was found between bacteria and bacteriophage richness in children with subsequent adequate/moderate growth. |
[13] |
IBD/humans | Fecal samples from 24 children, 12 with inflammatory bowel disease and 12 controls | Identification of viral sequences and bacterial microbiota sequencing | -Caudovirales’ relative abundance was greater than that of Microviridae in both inflammatory bowel disease patients and healthy controls. -Caudovirales was more abundant in Chron´s disease patients than in ulcerative colitis patients, but not than in control patients. -Pediatric inflammatory bowel disease patients can be distinguished from healthy controls by bacterial community composition. |
[14] |
Crohn´s disease/mice | 12–23 BALB/CYJ mice | Disruption of normal resident microbiota with streptomycin sulphate administration and phage therapy | -A single day of treatment with a phage cocktail significantly decreased the number of adherent invasive Escherichia coli in feces. -A single dose of the phage cocktail reduced dextran sodium sulphate-induced colitis symptoms in mice. |
[15] |
Colorectal cancer (CRC) and colonic adenoma/humans | 71 colorectal cancer patients, 63 adenoma patients, and 91 healthy controls | Metagenomic sequencing of the gut microbiome and microbial interactions in adenoma and colorectal cancer patients | -Uncultured CrAssphage was higher in healthy controls and positively associated with beneficial butyrate-producing bacteria in gut microbiota (GM). -GV was much more dynamic than the GM as the disease progressed. |
[16] |
CRC/humans | 90 human subjects, (30 healthy controls, 30 of whom had adenomas, and 30 of whom had carcinomas) | Stool samples analyzed by 16S rRNA gene, whole shotgun metagenomics, and purified virus metagenomic sequencing | -The CRC-associated GV consisted primarily of temperate bacteriophages. -Phages influenced cancer by directly modulating the influential bacteria. |
[17] |
Enteric pathogens/mice | 100 C57BL/6J mice | Viruses generated from molecular clones were used to infect cell lines to liberate virions. Subsequently, clones were used to infect mice that were euthanized and investigated for results of viral infections | -Chronic murine astrovirus complements defects in adaptive immunity by elevating cell-intrinsic IFN-λ in the intestinal epithelial barrier in immunodeficient mice. -Elements of the GV can protect against enteric pathogens in an immunodeficient host. |
[18] |
Alcoholic hepatitis/humans | 89 patients with alcoholic hepatitis, 36 with alcohol use disorder, and 17 healthy people as controls | Metagenomic sequencing of virus-like particles from fecal samples, fractionated using differential filtration techniques | -Patients with alcohol use disorder showed increased viral diversity in fecal samples compared to controls and patients with alcoholic hepatitis. -History of antibiotic treatment was associated with higher GV diversity. -Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased hepatic disease severity. |
[19] |
Viral entities/humans | 662 samples from 1-year-old children | Processing of metagenomics and metaviromics datasets | -Viral enrichment during sample processing showed a loss of a significant part of the GV and did not represent integrated bacteria containing dormant phages (prophagues). -Approximately 65–83% of the viral populations in the metavirome were not aligned with the metagenome data. |
[20] |
Nonalcoholic fatty liver diseases (NAFLD)/humans | 73 patients with NAFLD | RNA and DNA virus-like particles from fecal samples | -Patients with NAFLD and cirrhosis showed a significant decrease in intestinal viral diversity compared with controls. -Advanced NAFLD was associated with a reduction in the proportion of phages compared with other intestinal viruses. |
[21] |
IBD/humans | 54 Patients with IBD and 23 healthy controls | Virus-like particles were purified from stool samples and characterized by DNA and RNA sequencing and VLP particle counts |
-Viral populations associated with IBD showed perturbations with respect to healthy controls. -Anelloviridae showed a higher prevalence in IBD compared to healthy controls, and Analloviridae DNA levels were biomarkers of the effectiveness of immunosuppression. -IBD subjects had a higher ratio of Caudovirales to Microviridae phages compared to healthy controls. |
[22] |
CRC/humans | 80 colorectal primary tumors tissues and corresponding normal colorectal tissues | GV and bacteriome analysis for CRC tissues | -The number of viral species increased whereas bacterial species decreased in CRC tissues compared with healthy ones. -Phages were the most preponderant viral species in CRC tissues, and the main families were Myoviridae, Siphoviridae, and Podoviridae. -Primary CRC tissues were enriched for Enterobacteria, Bacillus, Proteus, and Streptococcus phages, together with their pathogenic hosts in contrast to normal tissues. |
[23] |
Type 2 diabetes (T2D)/humans | 71 T2D patients and 74 healthy controls | Whole-community metagenomic sequencing data of fecal samples | -Significant increase in the number of gut phages in fecal samples was found in the T2D group. -Significant alterations of the gut phageome cannot be explained simply by covariation with the altered bacterial hosts. |
[24] |
Cognitive maintenance/humans | 120 subjects, 60 with obesity and 60 without obesity | Neuropsychological assessment in humans, extraction of fecal genomic DNA and whole-genome shotgun sequencing | -GV was dominated by Caudovirales and Microviridae phages. -Subjects with increased Caudovirales and Siphoviridae levels in the gut microbiome performed better cognitive status. -Phages should be considered novel actors in the microbiome–brain axis. |
[24] |
Cognitive maintenance/mice | 11 mice were orally gavaged with saline and fecal material from humans | Behavioral testing in mice and study of gene expression in mouse prefrontal cortex | -Microbiota transplantation from human donors with increased specific Caudovirales levels led to increased scores in novel object recognition. -Phages should be considered novel actors in the microbiome–brain axis. |
[25] |
CRC/humans | 74 patients with CRC and 92 healthy controls | Shotgun metagenomic analyses of viromes of fecal samples | -Gut phage community diversity was significantly increased in patients with CRC compared with controls. -GV dysbiosis was associated with early- and late-stage CRC. |
[26] |
Fructose intake/mice | 25 C57BL/6J mice per group were used for phage production, and 36 mice were used for the in vivo dietary crossover study | Lactobacillus reuteri survival and phage production during gastrointestinal transit in mice | -Fructose intake activated the Ack pathway, involved in generating acetic acid, which promotes phage production. | [27] |
Malnutrition/humans | 8 monozygotic and 12 dizygotic twin pairs | Shotgun pyrosequencing of VLP-derived DNA | -Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. | [28] |
Type 1 diabetes (T1D)/humans | 103 T1D children and their mothers | Determination of virus antibodies, enterovirus RNA, and enzyme immunoassay analysis | -Autoantibody-positive children had more enterovirus infections than autoantibody-negative children before the appearance of autoantibodies. -Enterovirus infections seem to be associated with the induction of β-cell autoimmunity in young children with increased genetic susceptibility to T1D. |
[29] |
High-fat diet/mice | 12 C57BL/6J pregnant female mice | Mice were administered with subtherapeutic antibiotic dosages or no antibiotic and subsequently analyzed for GV composition and 16S rRNA metagenomics | -High-fat diet significant shift away from the relatively abundant Siphoviridae, accompanied by increases in phages from the Microviridae family. -Phage structural genes significantly decreased after the transition to a high-fat diet. |
[30] |
IBD/humans and mice | Fecal samples collected from 3 ulcerative colitis patients in remission and 3 unrelated healthy controls were transferred to C57BL/6 mice | Fecal virus-like particles (VLPs) isolated from ulcerative colitis patients and healthy controls were transferred to mice | -VLPs isolated from ulcerative colitis patients specifically altered the relative abundances of several bacterial taxa involved in IBD progression in mice. -Phages are dynamic regulators of GM and implicate the GV in modulating intestinal inflammation and disease. |
[31] |
T1D/humans | Fecal samples from 11 children who had developed serum autoantibodies associated with T1D and healthy controls | Detection of phage and eukaryotic viral sequences | -GV of T1D subjects was less diverse than those of controls. Lower phage diversity in cases than in controls. -Specific components of the GV were both directly and inversely associated with the development of human autoimmune disease. -Among eukaryotic viruses, there was a significant enrichment of Circoviridae-related sequences in controls in comparison with T1D patients. |
[32] |
Hypertension/humans | 196 samples | Viral and bacterial metagenomic investigation of fecal samples | -Virus could have higher discrimination power than bacteria to differentiate healthy prehypertension samples from hypertension patients | [33] |