Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota

Abstract Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizoph...

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Main Authors: Ying Qing, Lihua Xu, Gaoping Cui, Liya Sun, Xiaowen Hu, Xuhan Yang, Jie Jiang, Juan Zhang, Tianhong Zhang, Tao Wang, Lin He, Jijun Wang, Chunling Wan
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:npj Schizophrenia
Online Access:https://doi.org/10.1038/s41537-021-00180-1
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author Ying Qing
Lihua Xu
Gaoping Cui
Liya Sun
Xiaowen Hu
Xuhan Yang
Jie Jiang
Juan Zhang
Tianhong Zhang
Tao Wang
Lin He
Jijun Wang
Chunling Wan
author_facet Ying Qing
Lihua Xu
Gaoping Cui
Liya Sun
Xiaowen Hu
Xuhan Yang
Jie Jiang
Juan Zhang
Tianhong Zhang
Tao Wang
Lin He
Jijun Wang
Chunling Wan
author_sort Ying Qing
collection DOAJ
description Abstract Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth–body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.
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spelling doaj.art-f6a6773f2b914f9588a276464f0bdbd52023-12-02T06:37:22ZengNature Portfolionpj Schizophrenia2334-265X2021-10-017111010.1038/s41537-021-00180-1Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiotaYing Qing0Lihua Xu1Gaoping Cui2Liya Sun3Xiaowen Hu4Xuhan Yang5Jie Jiang6Juan Zhang7Tianhong Zhang8Tao Wang9Lin He10Jijun Wang11Chunling Wan12Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityShanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic DisordersBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityShanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic DisordersDepartment of Bioinformatics and Biostatistics, Shanghai Jiao Tong UniversityBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityShanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic DisordersBio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong UniversityAbstract Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth–body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.https://doi.org/10.1038/s41537-021-00180-1
spellingShingle Ying Qing
Lihua Xu
Gaoping Cui
Liya Sun
Xiaowen Hu
Xuhan Yang
Jie Jiang
Juan Zhang
Tianhong Zhang
Tao Wang
Lin He
Jijun Wang
Chunling Wan
Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
npj Schizophrenia
title Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
title_full Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
title_fullStr Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
title_full_unstemmed Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
title_short Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota
title_sort salivary microbiome profiling reveals a dysbiotic schizophrenia associated microbiota
url https://doi.org/10.1038/s41537-021-00180-1
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