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

Abstract

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.

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response

“…Lactobacillus group bacterial numbers correlated positively with severity of psychotic symptoms and negatively with global assessment of functioning. The increased levels of lactobacilli in FEP patients are consistent with reports in autistic children (Adams et al, 2011) and with reports showing increased abundance of bacteriophage genome of Lactobacillus phage phiadh in human oropharyngeal samples of schizophrenia patients (Yolken et al, 2015).…”

The Central Nervous System and the Gut Microbiome

“…Higher incidence of lactic-acid bacteria in the oropharyngeal microbiome was reported, compared to controls (Castro-Nallar et al, 2015). Interestingly, a Lactobacillus specific phage was also discovered in high abundance (Yolken et al, 2015). Another study reported a blood-specific microbiome in schizophrenia patients, compared to controls, with higher alpha and beta diversity (Mangul et al, 2016; Severance et al, 2013).…”

May the Force Be With You: The Light and Dark Sides of the Microbiota–Gut–Brain Axis in Neuropsychiatry

“…Bacteriophages infect bacteria and subsequently alter their metabolism and replication, which could affect the composition of the microbiota and their ability to signal to the brain. The levels of the bacteriophage Lactobacillus phage phiadh were found to be elevated in the oropharyngeal microbiota in schizophrenic patients with comorbid immunological conditions [160]. The main Lactobacillus host for this bacteriophage is Lactobacillus gasseri , a strain of bacteria that is found in the oral and gastrointestinal mucosae and is linked with host immune modulation [161].…”