Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children

 "Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease."



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Viral Soldiers | The Scientist Magazine®

A nice review of the potential antimicrobial use of bacteriophages.

Metagenomic Sequencing Indicates That the Oropharyngeal Phageome of Individuals With Schizophrenia Differs From That of Controls.

Mucosal sites such as the oropharynx contain a wide range of microorganisms, collectively designated as the microbiome. The microbiome can affect behavior through a number of neurobiological and immunological mechanisms. Most previous studies have focused on the bacterial components of the microbiome. However, the microbiome also includes viruses such as bacteriophages, which are viruses that infect bacteria and alter their metabolism and replication. We employed metagenomic analysis to characterize bacteriophage genomes in the oral pharynx of 41 individuals with schizophrenia and 33 control individuals without a psychiatric disorder. This analysis was performed by the generation of more than 100000000 sequence reads from each sample and the mapping of these reads to databases. We identified 79 distinct bacteriophage sequences in the oropharyngeal samples. Of these, one bacteriophage genome, Lactobacillus phage phiadh, was found to be significantly different in individuals with schizophrenia (P < .00037, q < 0.03 adjusted for multiple comparisons). The differential levels of Lactobacillus phage phiadh remained significant when controlling for age, gender, race, socioeconomic status, or cigarette smoking (P < .006). Within the group of individuals with schizophrenia, the level of Lactobacillus phage phiadh correlated with the prevalence of immunological disorders as well as with the administration of valproate, which has been shown in animal models to alter the microbiome. The bacteriophage composition of the oropharynx in individuals with schizophrenia differs from that of controls. The biological consequences of this difference and the potential effects of altering bacteriophage levels through therapeutic interventions are worthy of further investigation.

Bacteriophage therapy for bacterial infections ?

Phages RULE, OK?!

Antibiotic Resistance Revitalizes Century-Old phage Therapy - Scientific American

For decades, patients behind the Iron Curtain were denied access to some of the best antibiotics developed in the West. To make do, the Soviet Union invested heavily in the use of bacteriophages — viruses that kill bacteria — to treat infections. Phage therapy is still widely used in Russia, Georgia and Poland, but never took off elsewhere. “This is a virus, and people are afraid of viruses,” says Mzia Kutateladze, who is the head of the scientific council at the Eliava Institute in Tbilisi, which has been studying phages and using them to treat patients for nearly a century.

Now, faced with the looming spectre of antibiotic resistance, Western researchers and governments are giving phages a serious look. In March, the US National Institute of Allergy and Infectious Diseases listed phage therapy as one of seven prongs in its plan to combat antibiotic resistance. And at the American Society for Microbiology (ASM) meeting in Boston last month, Grégory Resch of the University of Lausanne in Switzerland presented plans for Phagoburn: the first large, multi-center clinical trial of phage therapy for human infections, funded by the European Commission.

Bacteriophages shuttle genes between diverse ecosystems.: Going Viral | The Scientist Magazine®

 "As little more than carriers of DNA, bacteriophages serve to shuttle genes between diverse ecosystems. The viruses take up genetic material from their bacterial hosts and donate it to future hosts, both near and far. Such genetic movement can spread bacterial traits such as virulence, antibiotic resistance, or adhesion capability—and even introduce novel genes to new environments. While viruses can only move short distances outside of a host, the migration of bacteria, or of the megafauna that bacteria infect, allows phages to traverse the globe."

Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome : Nature : Nature Publishing Group

The mammalian gut ecosystem has considerable influence on host physiology but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to the gut ecosystem, such as through antibiotic treatment or diet, are at present interpreted at the level of bacterial phylogeny. Less is known about the contributions of the abundant population of phages to this ecological network. Here we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine faecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug, as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phages from treated mice provide aerobically cultured naive microbiota with increased resistance. Systems-wide analyses uncovered post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome becomes broadly enriched for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage–bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance, and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.

Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome : Nature : Nature Publishing Group

The mammalian gut ecosystem has considerable influence on host physiology, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to the gut ecosystem, such as through antibiotic treatment or diet, are at present interpreted at the level of bacterial phylogeny. Less is known about the contributions of the abundant population of phages to this ecological network. Here we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine faecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug, as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phages from treated mice provide aerobically cultured naive microbiota with increased resistance. Systems-wide analyses uncovered post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome becomes broadly enriched for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage–bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance, and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.

ScienceDirect.com - Virology - What is needed for phage therapy to become a reality in Western medicine?

B0007272 Bacteriophage (Photo credit: wellcome images)

The current status of phage therapy approaches is reviewed and possible hurdles to a practical medical application of bacteriophages in Western countries are identified as discussed at a recent EMBO meeting on “Viruses of Microbes” in Brussels. In view of the growing antibiotic resistance crisis, a coordinated effort by the public health sector is needed to evaluate the potential of phage therapy as an adjunct to antibiotics.

New immune system discovered

"Taking previous research into consideration, we are able to propose the Bacteriophage Adherence to Mucus—or BAM—is a new model of immunity, which emphasizes the important role bacteriophage play in protecting the body from invading pathogens"

Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome.

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

Turning a new phage : Using phages as antibiotics: Nature Medicine :

The idea of using bacteria-fighting viruses as a weapon against hard-to-treat infections is making a surprising comeback, but with a twist on how it has been attempted for nearly a century. Researchers and companies are now tweaking and deconstructing these bacteria killers in an effort to develop a new arsenal against antibiotic-resistant superbugs—one with more potency and a better likelihood of regulatory approval. 
Bacteriophage Wikipedia

Video from A BBC2 Horizon programme (1997): The Virus that Cures – Documentary about the history of phage medicine in Russia and the West