Altered oral microbiota and immune dysfunction in Chinese elderly patients with schizophrenia: a cross-sectional study.

Schizophrenia (SZ) is a complex psychiatric neurodevelopmental disorder with uncertain etiology and pathogenesis. Increasing evidence has recognized the key role of the gut microbiota in SZ. However, few studies have investigated the potential link between oral microbiota and SZ. We studied the tongue coating microbiota and inflammatory profiles of 118 elderly SZ patients and 97 age-matched healthy controls using Illumina MiSeq sequencing and multiplex immunoassays, respectively. Reduced α-diversity, along with a significant difference in ß-diversity, were observed in patients with SZ. We have identified SZ-associated oral dysbiosis, characterized by increased Streptococcus and Fusobacterium, as well as decreased Prevotella and Veillonella. These differential genera could potentially serve as biomarkers for SZ, either alone or in combination. Additionally, an elevated Streptococcus/Prevotella ratio could indicate oral dysbiosis. These differential genera formed two distinct clusters: Streptococcus-dominated and Prevotella-dominated, which exhibited different correlations with the altered immunological profiles. Furthermore, we also observed disruptions in the inferred microbiota functions in SZ-associated microbiota, particularly in lipid and amino acid metabolism. Our study provides novel insights into the characteristics of tongue coating microbiota and its associations with immunological disturbances in elderly SZ patients, which offer new targets for the diagnosis and treatment of SZ in the elderly.

A comparative study to determine the association of gut microbiome with schizophrenia in Zhejiang, China.

BACKGROUND: With the rapid progress of high-throughput sequencing technology, characterization of schizophrenia (SZ) with underlying probing of the gut microbiome can explore pathogenic mechanisms, estimate disease risk, and allow customization of therapeutic and prophylactic modalities. In this study, we compared the differences in gut microbial diversity and composition between 50 SZ subjects and 50 healthy matched subjects in Zhejiang, China via targeted next-generation sequencing (16S rRNA amplicon). RESULTS: Accordingly, the alpha diversity indices (observed species index, Shannon index, and Simpson index) of the gut microbiome in the healthy control group were higher than those in the SZ group. Additionally, principal coordinate analysis and non-metric multidimensional scaling of beta diversity revealed that patients with SZ clustered more tightly than healthy controls. At the phylum level, we found that the abundance of Bacteroidetes and Proteobacteria in the SZ group was significantly increased. At the genus level, the relative abundances of Prevotella, Parabacteroides, and Sutterella were significantly higher, whereas the abundances of Faecalibacterium, Blautia, Lachnospira, Clostridium, Ruminococcus, and Coprococcus were lower than those in the healthy control group. Further analyses revealed that Succinivibrio, Megasphaera, and Nesterenkonia may serve as potential biomarkers for distinguishing patients with SZ from those in the control cohort. CONCLUSIONS: This study profiled differences in gut microbiome diversity, taxonomic composition, and function between SZ and healthy cohorts, and the insights from this research could be used to develop targeted next-generation sequencing-based diagnoses for SZ.

Changes in fecal microbiota composition and the cytokine expression profile in school-aged children with depression: A case-control study.

Depression in childhood negatively affects the growth and development, school performance, and peer or family relationships of affected children, and may even lead to suicide. Despite this, its etiology and pathophysiology remain largely unknown. Increasing evidence supports that gut microbiota plays a vital role in the development of childhood depression. However, little is known about the underlying mechanisms, as most clinical studies investigating the link between gut microbiota and depression have been undertaken in adult cohorts. In present study, a total of 140 school-aged children (6-12 years) were enrolled, including 92 with depression (male/female: 42/50) and 48 healthy controls (male/female: 22/26) from Lishui, Zhejiang, China. Illumina sequencing of the V3-V4 region of the 16S rRNA gene was used to investigate gut microbiota profiles while Bio-Plex Pro Human Cytokine 27-plex Panel was employed to explore host immune response. We found that, compared with healthy controls, children with depression had greater bacterial richness and altered ß-diversity. Pro-inflammatory genera such as Streptococcus were enriched in the depression group, whereas anti-inflammatory genera such as Faecalibacterium were reduced, as determined by linear discriminant analysis effect size. These changes corresponded to altered bacterial functions, especially the production of immunomodulatory metabolites. We also identified the presence of a complex inflammatory condition in children with depression, characterized by increased levels of pro-inflammatory cytokines such as IL-17 and decreased levels of anti-inflammatory cytokines such as IFN-γ. Correlation analysis demonstrated that the differential cytokine abundance was closely linked to changes in gut microbiota of children with depression. In summary, key functional genera, such as Streptococcus and Faecalibacterium, alone or in combination, could serve as novel and powerful non-invasive biomarkers to distinguish between children with depression from healthy ones. This study was the first to demonstrate that, in Chinese children with depression, gut microbiota homeostasis is disrupted, concomitant with the activation of a complex pro-inflammatory response. These findings suggest that gut microbiota might play an important role in the pathogenesis of depression in school-aged children, while key functional bacteria in gut may serve as novel targets for non-invasive diagnosis and patient-tailored early precise intervention in children with depression.

Fecal Dysbiosis and Immune Dysfunction in Chinese Elderly Patients With Schizophrenia: An Observational Study.

Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial ß-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1ß were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.