Altered gut microbiota and systemic immunity in Chinese patients with schizophrenia comorbid with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis. METHODS AND RESULTS: We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in ß-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera. CONCLUSION: These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.

Gut microbiome and metabolism alterations in schizophrenia with metabolic syndrome severity.

BACKGROUND: Schizophrenia (SCZ) patients undergoing antipsychotic treatment demonstrated a high prevalence and harmful effects of metabolic syndrome (MetS), which acted as the major cause of cardiovascular disease. The major clinical challenge is the lack of biomarkers to identify MetS episodes and prevent further damage, while the mechanisms underlying these drug-induced MetS remain unknown. METHODS: This study divided 173 participants with SCZ into 3 groups (None, High risk, and MetS, consisting of 22, 88, and 63 participants, respectively). The potential biomarkers were searched based on 16S rRNA gene sequence together with metabolism analysis. Logistic regression was used to test the effects of the genus-metabolites panel on early MetS diagnoses. RESULTS: A genus-metabolites panel, consisting of Senegalimassilia, sphinganine, dihomo-gamma-linolenoylcholine, isodeoxycholic acid, and MG (0:0/22:5/0:0), which involved in sphigolipid metabolism, fatty acid metabolism, secondary bile acid biosynthesis and glycerolipid metabolism, has a great discrimination efficiency to MetS with an area under the curve (AUC) value of 0.911 compared to the None MetS group (P = 1.08E-8). Besides, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) distinguished between subgroups robustly and exhibited a potential correlation with the severity of MetS in patients with SCZ, and may act as the biomarkers for early MetS diagnosis. CONCLUSIONS: Our multi-omics study showed that one bacterial genus-five lipid metabolites panel is the potential risk factor for MetS in SCZ. Furthermore, Senegalimassilia, 3-Hydroxytetradecanoyl carnitine, isodeoxycholic acid, and DG(TXB2/0:0/2:0) could serve as novel diagnostic markers in the early stage. So, it is obvious that the combination of bacterial genus and metabolites yields excellent discriminatory power, and the lipid metabolism provide new understanding to the pathogenesis, prevention, and therapy for MetS in SCZ.

Intestinal mycobiota dysbiosis associated inflammation activation in chronic schizophrenia.

The microbiome-gut-brain axis is related to schizophrenia (SCZ). The role of intestinal mycobiota in SCZ has been under investigated. We present a half-year follow-up study involving 109 chronic SCZ patients and 77 healthy controls. Intestinal mycobiota was tested by internal transcribed spacer (ITS). Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal metabolites. Symptom severity was assessed using the Positive and Negative Syndrome Scale. Enterotype analysis showed that Candida-type patients exhibited severer positive symptoms and depression factors than Saccharomyces-type patients. Candida and its top species and operational taxonomic units (OTUs) were positively correlated with depression factors (all p=0.001). Fecal metabolites analysis showed that upregulated metabolites were associated with chronic inflammation (NF-κB pathway and T helper cell differentiation), downregulated metabolites were associated with glutamate metabolism, serotonergic and dopaminergic synapse. Procrustes analysis revealed significant correlation between intestinal mycobiota and fecal metabolites (M2=0.937, p<0.001). Metabolic module analysis showed that the top module, MEturquoise (associated with Th1 and Th2 cell differentiation), was negatively correlated with SCZ (r=-0.783, p<0.0001), positively correlated with Candida, Aspergillus, Trichosporon and Talaromyces (decreased in SCZ) and negatively correlated with Saccharomyces (increased in SCZ). We also found impairments of intestinal barrier in SCZ, characterized by increased in blood D-lactate (mucosa impairment marker) and decreased in blood mucin 2 (mucosal barrier protective protein). Serum levels of TNF-α was increased and showed stable high levels during treatment. This study suggests that mycobiota dysbiosis-related chronic inflammation and an impaired intestinal mucosal barrier are associated with chronic SCZ.

Reproducible gut microbial signatures in bipolar and schizophrenia spectrum disorders: A metagenome-wide study.

BACKGROUND: Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders. METHODS: In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol. RESULTS: The gut microbiome of the patients had a significantly different ß-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use. CONCLUSIONS: Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use.

Multi-omics analysis reveals the impact of gut microbiota on antipsychotic-induced weight gain in schizophrenia.

Emerging evidence indicates that gut microbial dysbiosis is associated with the development of antipsychotic-induced weight gain in schizophrenia (SZ). However, the exact taxonomic composition and functionality that constitute the "obesogenic" microbial profile remain elusive. Our retrospective survey identified two groups of the SZ population separated by BMI, with 1/3 of patients developing overweight/obesity after chronic antipsychotic treatment. Based on multi-omics analysis, we observed altered gut microbiota in SZ patients with overweight/obesity, characterized by a reduction in several beneficial bacteria genera, including Bacteroides, Parabacteroides, Akkermansia, and Clostridium. This microbial dysbiosis was accompanied by disrupted energy expenditure and nutritional metabolism, worsened metabolic indices, and reduced levels of beneficial metabolites, e.g. indole-3-carboxylic acid and propionic acid. Moreover, leveraging data from first-episode drug-naïve schizophrenia (FSZ) patients at one-month and one-year follow-up, both artificial neural network and random forest classifier-based prediction models demonstrated a strong ability of microbial profiles to predict antipsychotic-induced weight gain. Importantly, FSZ patients with higher relative abundance of Parabacteria distasonis were less susceptible to antipsychotic-induced weight gain. Thus, gut microbiota could serve as a noninvasive approach to predict antipsychotic-induced weight gain, guiding clinical antipsychotics administration and developing novel therapeutic strategies for weight management in SZ.

Association between the oral microbiome and brain resting state connectivity in schizophrenia.

Recent microbiome-brain axis findings have shown evidence of the modulation of microbiome community as an environmental mediator in brain function and psychiatric illness. This work is focused on the role of the microbiome in understanding a rarely investigated environmental involvement in schizophrenia (SZ), especially in relation to brain circuit dysfunction. We leveraged high throughput microbial 16s rRNA sequencing and functional neuroimaging techniques to enable the delineation of microbiome-brain network links in SZ. N = 213 SZ and healthy control subjects were assessed for the oral microbiome. Among them, 139 subjects were scanned by resting-state functional magnetic resonance imaging (rsfMRI) to derive brain functional connectivity. We found a significant microbiome compositional shift in SZ beta diversity (weighted UniFrac distance, p = 6 × 10-3; Bray-Curtis distance p = 0.021). Fourteen microbial species involving pro-inflammatory and neurotransmitter signaling and H2S production, showed significant abundance alterations in SZ. Multivariate analysis revealed one pair of microbial and functional connectivity components showing a significant correlation of 0.46. Thirty five percent of microbial species and 87.8 % of brain functional network connectivity from each component also showed significant differences between SZ and healthy controls with strong performance in classifying SZ from healthy controls, with an area under curve (AUC) = 0.84 and 0.87, respectively. The results suggest a potential link between oral microbiome dysbiosis and brain functional connectivity alteration in relation to SZ, possibly through immunological and neurotransmitter signaling pathways and the hypothalamic-pituitary-adrenal axis, supporting for future work in characterizing the role of oral microbiome in mediating effects on SZ brain functional activity.

Meta-analysis of the human gut microbiome uncovers shared and distinct microbial signatures between diseases.

Microbiome studies have revealed gut microbiota's potential impact on complex diseases. However, many studies often focus on one disease per cohort. We developed a meta-analysis workflow for gut microbiome profiles and analyzed shotgun metagenomic data covering 11 diseases. Using interpretable machine learning and differential abundance analysis, our findings reinforce the generalization of binary classifiers for Crohn's disease (CD) and colorectal cancer (CRC) to hold-out cohorts and highlight the key microbes driving these classifications. We identified high microbial similarity in disease pairs like CD vs ulcerative colitis (UC), CD vs CRC, Parkinson's disease vs type 2 diabetes (T2D), and schizophrenia vs T2D. We also found strong inverse correlations in Alzheimer's disease vs CD and UC. These findings, detected by our pipeline, provide valuable insights into these diseases. IMPORTANCE: Assessing disease similarity is an essential initial step preceding a disease-based approach for drug repositioning. Our study provides a modest first step in underscoring the potential of integrating microbiome insights into the disease similarity assessment. Recent microbiome research has predominantly focused on analyzing individual diseases to understand their unique characteristics, which by design excludes comorbidities in individuals. We analyzed shotgun metagenomic data from existing studies and identified previously unknown similarities between diseases. Our research represents a pioneering effort that utilizes both interpretable machine learning and differential abundance analysis to assess microbial similarity between diseases.

Perturbations in gut microbiota composition in schizophrenia.

Schizophrenia is a severe, complex and long-term psychiatric disorder with unclear etiology. Gut microbes influence the central nervous system via the gut-brain axis. Consequently, investigations of the relationship between gut microbes and schizophrenia are warranted. This study involved 29 patients with schizophrenia and 30 age-matched normal controls. After 16S rRNA gene sequencing and whole-genome shotgun metagenomic sequencing, we analyzed microbial diversity, composition, and function. According to 16S rRNA and metagenomic gene sequencing results, patients with schizophrenia had higher abundances of Clostridium and Megasphaera. Functional analysis showed that sphingolipid, phosphonates and phosphinates, as well as glutamine metabolism were associated with the occurrence and development of schizophrenia. Our data suggest that the gut microbiota exerts an effect on patients with schizophrenia, providing valuable insights into the potential regulation of in the context of this disorder.

16S rRNA gene sequencing reveals altered gut microbiota in young adults with schizophrenia and prominent negative symptoms.

BACKGROUND: Gut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH-N) in young adults have been poorly elucidated. METHODS: Stool samples were obtained from 30 young adults with SCH-N, 32 SCH patients with prominent positive symptoms (SCH-P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). RESULTS: There is a significant difference in ß-diversity but not α-diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH-N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia-Shigella, Dorea, and Butyricicoccus) that can distinguish SCH-N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH-N and SCH-P is much less than that between SCH-N and the HC, and SCH-N and SCH-P cannot be effectively distinguished by gut microbiota. CONCLUSION: The composition of gut microbiota was changed in the patients with SCH-N, which may help in further understanding of pathogenesis in young adults with SCH-N.

Cognition and gut microbiota in schizophrenia spectrum and mood disorders: A systematic review.

FRILEUX, M., BOLTRI M. and al. Cognition and Gut microbiota in schizophrenia spectrum and mood disorders: a Systematic Review. NEUROSCI BIOBEHAV REV (1) 2024 Schizophrenia spectrum disorders and major mood disorders are associated with cognitive impairments. Recent studies suggest a link between gut microbiota composition and cognitive functioning. Here, we review the relationship between gut microbiota and cognition in these disorders. To do this, we conducted a systematic review, searching Cochrane Central Register of Controlled Trials, EBSCOhost, Embase, Pubmed, Scopus, and Web of Science. Studies were included if they investigated the relationship between gut microbiota composition and cognitive function through neuropsychological assessments in patients with bipolar, depressive, schizophrenia spectrum, and other psychotic disorders. Ten studies were identified. Findings underscore a link between gut dysbiosis and cognitive impairment. This relationship identified specific taxa (Haemophilus, Bacteroides, and Alistipes) as potential contributors to bolstered cognitive performance. Conversely, Candida albicans, Toxoplasma gondii, Streptococcus and Deinococcus were associated with diminished performance on cognitive assessments. Prebiotics and probiotics interventions were associated with cognitive enhancements, particularly executive functions. These results emphasize the role of gut microbiota in cognition, prompting further exploration of the underlying mechanisms paving the way toward precision psychiatry.

The relationship between the gut microbiota and oxidative stress in the cognitive function of schizophrenia: A pilot study in China.

Cognitive impairment is a core symptom of schizophrenia. The gut microbiota (GM) and oxidative stress may play important roles in the pathophysiological mechanisms of cognitive impairment. This study aimed to explore the relationship between GM and oxidative stress in the cognitive function of schizophrenia. GM obtained by 16S RNA sequencing and serum superoxide dismutase (SOD) levels from schizophrenia patients (N = 68) and healthy controls (HCs, N = 72) were analyzed. All psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Correlation analysis was used to explore the relationship between GM, SOD, and cognitive function. Machine learning models were used to identify potential biomarkers. Compared to HCs, the relative abundances of Collinsella, undefined Ruminococcus, Lactobacillus, Eubacterium, Mogibacterium, Desulfovibrio, Bulleidia, Succinivibrio, Corynebacterium, and Atopobium were higher in patients with schizophrenia, but Faecalibacterium, Anaerostipes, Turicibacter, and Ruminococcus were lower. In patients with schizophrenia, the positive factor, general factor, and total score of MCCB positively correlated with Lactobacillus, Collinsella, and Lactobacillus, respectively; SOD negatively correlated with Eubacterium, Collinsella, Lactobacillus, Corynebacterium, Bulleidia, Mogibacterium, and Succinivibrio, but positively correlated with Faecalibacterium, Ruminococcus, and MCCB verbal learning index scores; Faecalibacterium and Turicibacter were positively correlated with MCCB visual learning index scores and speed of processing index scores, respectively. Our findings revealed a correlation between SOD and GM and confirmed that cognitive dysfunction in patients with schizophrenia involves abnormal SOD levels and GM changes.

The Gut-Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production.

Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal mental function and behavior. Its multifactorial etiology involves genetic factors, experiences of adversity, infection, and gene-environment interactions. Emerging research indicates that maternal infection or stress during pregnancy may also increase schizophrenia risk in offspring. Recent research on the gut-brain axis highlights the gut microbiome's potential influence on central nervous system (CNS) function and mental health, including schizophrenia. The gut microbiota, located in the digestive system, has a significant role to play in human physiology, affecting immune system development, vitamin synthesis, and protection against pathogenic bacteria. Disruptions to the gut microbiota, caused by diet, medication use, environmental pollutants, and stress, may lead to imbalances with far-reaching effects on CNS function and mental health. Of interest are short-chain fatty acids (SCFAs), metabolic byproducts produced by gut microbes during fermentation. SCFAs can cross the blood-brain barrier, influencing CNS activity, including microglia and cytokine modulation. The dysregulation of neurotransmitters produced by gut microbes may contribute to CNS disorders, including schizophrenia. This review explores the potential relationship between SCFAs, the gut microbiome, and schizophrenia. Our aim is to deepen the understanding of the gut-brain axis in schizophrenia and to elucidate its implications for future research and therapeutic approaches.

The association between greenery type and gut microbiome in schizophrenia: did all greenspaces play the equivalent role?

In recent years, attention has been focused on the benefit of greenspace on mental health, and it is suggested this link may vary with the type of greenspace. More and more studies have emphasized the influence of the gut microbiome on schizophrenia (SCZ). However, the effects of greenspaces on the gut microbiota in SCZ and the effect of different types of greenspaces on the gut microbiota remain unclear. We aim to examine if there were variations in the effects of various greenspace types on the gut microbiome in SCZ. Besides, we sink to explore important taxonomic compositions associated with different greenspace types. We recruited 243 objects with schizophrenia from Anhui Mental Health Center and collected fecal samples for 16Sr RNA gene sequencing. Three types of greenery coverage were calculated with different circular buffers (800, 1500, and 3000 m) corresponding to individual addresses. The association between greenspace and microbiome composition was analyzed with permutational analysis of variance (PERMANOVA). We conducted the linear regression to capture specific gut microbiome taxa associated with greenery coverage. Tree coverage was consistently associated with microbial composition in both 1500 m (R2 = 0.007, P = 0.030) and 3000 m (R2 = 0.007, P = 0.039). In contrast, there was no association with grass cover in any of the buffer zones. In the regression analysis, higher tree coverage was significantly correlated with the relative abundance of several taxa. Among them, tree coverage was positively associated with increased Bifidobacterium longum (ß = 1.069, P = 0.004), which was the dominant composition in the gut microbiota. The relationship between greenspace and gut microbiome in SCZ differed by the type of greenspace. Besides, "tree coverage" may present a dominant effect on the important taxonomic composition. Our findings might provide instructive evidence for the design of urban greenspace to optimize health and well-being in SCZ as well as the whole people.

Profiling gut microbiota signatures associated with the deficit subtype of schizophrenia: Findings from a case-control study.

BACKGROUND: Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). METHODS: A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled. Gut microbiota was analyzed using the 16 rRNA amplicon sequencing. Additionally, the levels of C-reactive protein (CRP), glucose and lipid metabolism markers were determined in the peripheral blood samples. RESULTS: Altogether 14 genera showed differential abundance in patients with D-SCZ compared to ND-SCZ and HCs, including Candidatus Soleaferrea, Eubacterium, Fusobacterium, Lachnospiraceae UCG-002, Lachnospiraceae UCG-004, Lachnospiraceae UCG-010, Libanicoccus, Limosilactobacillus, Mogibacterium, Peptococcus, Prevotella, Prevotellaceae NK3B31 group, Rikenellaceae RC9 gut group, and Slackia after adjustment for potential confounding factors. Observed alterations were significantly associated with cognitive performance in both groups of patients. Moreover, several significant correlations of differentially abundant genera with the levels of CRP, lipid profile parameters, glucose and insulin were found across all subgroups of participants. CONCLUSION: Findings from the present study indicate that individuals with D-SCZ show a distinct profile of gut microbiota alterations that is associated with cognitive performance, metabolic parameters and subclinical inflammation.

Gut and oral microbiome modulate molecular and clinical markers of schizophrenia-related symptoms: A transdiagnostic, multilevel pilot study.

Although increasing evidence links microbial dysbiosis with the risk for psychiatric symptoms through the microbiome-gut-brain axis (MGBA), the specific mechanisms remain poorly characterized. In a diagnostically heterogeneous group of treated psychiatric cases and nonpsychiatric controls, we characterized the gut and oral microbiome, plasma cytokines, and hippocampal inflammatory processes via proton magnetic resonance spectroscopic imaging (1H-MRSI). Using a transdiagnostic approach, these data were examined in association with schizophrenia-related symptoms measured by the Positive and Negative Syndrome Scale (PANSS). Psychiatric cases had significantly greater heterogeneity of gut alpha diversity and an enrichment of pathogenic taxa, like Veillonella and Prevotella, in the oral microbiome, which was an accurate classifier of phenotype. Cases exhibited significantly greater positive, negative, and general PANSS scores that uniquely correlated with bacterial taxa. Strong, positive correlations of bacterial taxa were also found with cytokines and hippocampal gliosis, dysmyelination, and excitatory neurotransmission. This pilot study supports the hypothesis that the MGBA influences psychiatric symptomatology in a transdiagnostic manner. The relative importance of the oral microbiome in peripheral and hippocampal inflammatory pathways was highlighted, suggesting opportunities for probiotics and oral health to diagnose and treat psychiatric conditions.

Comparison of gut microbiome profile in patients with schizophrenia and healthy controls - A plausible non-invasive biomarker?

The human gut microbiome regulates brain function through the microbiome-gut-brain axis and is implicated in several neuropsychiatric disorders. However, the relationship between the gut microbiome and the pathogenesis of schizophrenia (SCZ) is poorly defined, and very few studies have examined the effect of antipsychotic treatment response. We aim to study the differences in the gut microbiota among drug-naïve (DN SCZ) and risperidone-treated SCZ patients (RISP SCZ), compared to healthy controls (HCs). We recruited a total of 60 participants, from the clinical services of a large neuropsychiatric hospital, which included DN SCZ, RISP SCZ and HCs (n = 20 each). Fecal samples were analyzed using 16s rRNA sequencing in this cross-sectional study. No significant differences were found in taxa richness (alpha diversity) but microbial composition differed between SCZ patients (both DN and RISP) and HCs (PERMANOVA, p = 0.02). Linear Discriminant Analysis Effect Size (LEfSe) and Random Forest model identified the top six genera, which significantly differed in abundance between the study groups. A specific genus-level microbial panel of Ruminococcus, UCG005, Clostridium_sensu_stricto_1 and Bifidobacterium could discriminate SCZ patients from HCs with an area under the curve (AUC) of 0.79, HCs vs DN SCZ (AUC: 0.68), HCs vs RISP SCZ (AUC: 0.93) and DN SCZ vs RISP SCZ (AUC: 0.87). Our study identified distinct microbial signatures that could aid in the differentiation of DN SCZ, RISP SCZ, and HCs. Our findings contribute to a better understanding of the role of the gut microbiome in SCZ pathophysiology and suggest potential targeted interventions.

Altered fecal microbiota composition in individuals who abuse methamphetamine.

As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Hidden Role of Gut Microbiome Dysbiosis in Schizophrenia: Antipsychotics or Psychobiotics as Therapeutics?

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively determined. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiology of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and production of postbiotics. Gut microbially produced molecules may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiology of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.

The gut microbiome is associated with brain structure and function in schizophrenia.

The effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = - 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = - 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = - 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.