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 100 000 000 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.