Altered gut microbiota associated with symptom severity in schizophrenia

Abstract

Background The gut microbiome and microbiome-gut-brain (MGB) axis have been receiving increasing attention for their role in the regulation of mental behavior and possible biological basis of psychiatric disorders. With the advance of next-generation sequencing technology, characterization of the gut microbiota in schizophrenia (SZ) patients can provide rich clues for the diagnosis and prevention of SZ. Methods In this study, we compared the differences in the fecal microbiota between 82 SZ patients and 80 demographically matched normal controls (NCs) by 16S rRNA sequencing and analyzed the correlations between altered gut microbiota and symptom severity. Results The alpha diversity showed no significant differences between the NC and SZ groups, but the beta diversity revealed significant community-level separation in microbiome composition between the two groups (pseudo-F =3.337, p < 0.001, uncorrected). At the phylum level, relatively more Actinobacteria and less Firmicutes (p < 0.05, FDR corrected) were found in the SZ group. At the genus level, the relative abundances of Collinsella, Lactobacillus, Succinivibrio, Mogibacterium, Corynebacterium, undefined Ruminococcus and undefined Eubacterium were significantly increased, whereas the abundances of Adlercreutzia, Anaerostipes, Ruminococcus and Faecalibacterium were decreased in the SZ group compared to the NC group (p < 0.05, FDR corrected). We performed PICRUSt analysis and found that several metabolic pathways differed significantly between the two groups, including the Polyketide sugar unit biosynthesis, Valine, Leucine and Isoleucine biosynthesis, Pantothenate and CoA biosynthesis, C5-Branched dibasic acid metabolism, Phenylpropanoid biosynthesis, Ascorbate and aldarate metabolism, Nucleotide metabolism and Propanoate metabolism pathways (p < 0.05, FDR corrected). Among the SZ group, the abundance of Succinivibrio was positively correlated with the total Positive and Negative Syndrome Scale (PANSS) scores (r = 0.24, p < 0.05, uncorrected) as well as the general PANSS scores (r = 0.22, p < 0.05, uncorrected); Corynebacterium was negatively related to the negative scores of PANSS (r = 0.22, p < 0.05, uncorrected). Conclusions Our findings provided evidence of altered gut microbial composition in SZ group. In addition, we found that Succinvibrio and Corynebacterium were associated with the severity of symptoms for the first time, which may provide some new biomarkers for the diagnosis of SZ.

The Gut Microbiome Was Associated With Brain Structure and Function in Schizophrenia

“…Furthermore, shifts in taxonomic abundance in SZs were consistent with previous studies. For instance, Roseburia (order Clostridiales) and Ruminococcus (order Lactobacillales) showed depletion in SZs, which was observed in multiple previous studies on psychiatric diseases 4,27,28 .…”

“…With the advent of sequencing technology, characterization of schizophrenia (SZ) with probing of the underlying gut microbiome can provide abundant clues for the diagnosis and prognosis of SZ 1 . Several published studies of the gut microbiome in SZ revealed that the species composition within the gut of individuals with SZ is different from that of normal control subjects (NCs), with varying bacterial taxa driving community separation in each study, and several of these studies have also focused on the relationship between different gut microbiota and clinical characteristics [2][3][4] . Converging evidence suggests that the gut microbiota communicates with the central nervous system bidirectionally through the microbiome-gut-brain (MGB) axis 5,6 .…”

Multi-biological Classification for the Diagnosis of Schizophrenia Using Multi-classifier, Multi-feature Selection and Multi-cross Validation: an Integrated Machine Learning Framework Study

“…The DNA extraction method was consistent with our previously published report [4] . Sequencing of the V4 region of the16S rRNA gene was performed on the Illumina MiSeq platform.…”

“…Finding effective and objective biomarkers to inform the diagnosis of schizophrenia (SZ) is of great importance yet remains challenging [1 2] . It is now broadly accepted that gut microbiota abundance, inflammation, immunological factors, and functional brain networks are altered in SZ [3][4][5][6] , however, most of these alterations are observed at the group level with great variability among individuals with the same phenotypic diagnosis Consequently, none so far has proven to have the ability to reliably aid in the differential diagnosis of SZ [1 7] . Therefore, it is important to analyze how gut microbiota abundance, inflammatory factors, immunological factors and functional brain networks behave at an individual level; for example, this information could be used to better understand the pathology and identify objective biomarkers for the clinical diagnosis of SZ [8] .…”

Anti-Inflammatory Diets and Schizophrenia

“…Alterations in microbiota composition and microbial metabolites affect gut integrity and immune responses. Gut dysbiosis was observed in patients with schizophrenia, and the abundance of specific bacterial genera, Succinivibrio and Corynebacterium , were significantly associated with the symptom severity of schizophrenia [ 64 ]. The gut dysbiosis may affect the susceptibility to infection and inflammation, which can accelerate the development of schizophrenia and aggravate its symptom severity.…”