Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls

Abstract

The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls were richer in species but less even in their distributions, i.e., dominated by fewer species, as opposed to schizophrenia patients. Lactic acid bacteria were relatively more abundant in schizophrenia, including species of Lactobacilli and Bifidobacterium, which have been shown to modulate chronic inflammation. We also found Eubacterium halii, a lactate-utilizing species. Functionally, the microbiome of schizophrenia patients was characterized by an increased number of metabolic pathways related to metabolite transport systems including siderophores, glutamate, and vitamin B12. In contrast, carbohydrate and lipid pathways and energy metabolism were abundant in controls. These findings suggest that the oropharyngeal microbiome in individuals with schizophrenia is significantly different compared to controls, and that particular microbial species and metabolic pathways differentiate both groups. Confirmation of these findings in larger and more diverse samples, e.g., gut microbiome, will contribute to elucidating potential links between schizophrenia and the human microbiota.

Keywords: Biomarkers; Functional diversity; Lactic acid bacteria; Metagenomics; Microbial abundance; Microbial diversity; Microbiome; PathoScope; Schizophrenia; Shotgun sequencing.

Figure 1. Oropharyngeal microbial composition at phylum and species levels exhibits different patterns for schizophrenia and control samples.

The stacked bar chart shows the most prevalent species present in schizophrenia and controls color-coded by phylum. Green, Actinobacteria; Orange, Bacteroidetes; Blue, Firmicutes; Green, Proteobacteria. The symbol (*) indicates samples from smoker individuals.

Figure 2. Covariation of community structure shows that diversity patterns of samples correlate with disease status, i.e., schizophrenia and controls, and potentially with smoking (at the genus level).

Points represent principal coordinate analysis (PCoA loadings) on Jensen–Shannon Diversity distances. Principal coordinates 1 and 2 in (A) (65% of variance) and principal coordinates 1 and 3 in (B) (63% of variance).

Figure 3. Microbial metabolic pathways with significantly altered abundances in the schizophrenia oropharyngeal microbiome.

MXXXXX codes correspond to KEGG modules, i.e., a collection of manually defined functional units (genes). LDA, linear discriminant analysis.