Epigenetic control of multiple genes with a lentiviral vector encoding transcriptional repressors fused to compact zinc finger arrays.

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.

Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.

Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.

Developmental prediction modeling based on diffusion tensor imaging uncovering age-dependent heterogeneity in early childhood autistic brain.

OBJECTIVE: There has been increasing evidence for atypical white matter (WM) microstructure in autistic people, but findings have been divergent. The development of autistic people in early childhood is clouded by the concurrently rapid brain growth, which might lead to the inconsistent findings of atypical WM microstructure in autism. Here, we aimed to reveal the developmental nature of autistic children and delineate atypical WM microstructure throughout early childhood while taking developmental considerations into account. METHOD: In this study, diffusion tensor imaging was acquired from two independent cohorts, containing 91 autistic children and 100 typically developing children (TDC), aged 4-7 years. Developmental prediction modeling using support vector regression based on TDC participants was conducted to estimate the WM atypical development index of autistic children. Then, subgroups of autistic children were identified by using the k-means clustering method and were compared to each other on the basis of demographic information, WM atypical development index, and autistic trait by using two-sample t-test. Relationship of the WM atypical development index with age was estimated by using partial correlation. Furthermore, we performed threshold-free cluster enhancement-based two-sample t-test for the group comparison in WM microstructures of each subgroup of autistic children with the rematched subsets of TDC. RESULTS: We clustered autistic children into two subgroups according to WM atypical development index. The two subgroups exhibited distinct developmental stages and age-dependent diversity. WM atypical development index was found negatively associated with age. Moreover, an inverse pattern of atypical WM microstructures and different clinical manifestations in the two stages, with subgroup 1 showing overgrowth with low level of autistic traits and subgroup 2 exhibiting delayed maturation with high level of autistic traits, were revealed. CONCLUSION: This study illustrated age-dependent heterogeneity in early childhood autistic children and delineated developmental stage-specific difference that ranged from an overgrowth pattern to a delayed pattern. Trial registration This study has been registered at ClinicalTrials.gov (Identifier: NCT02807766) on June 21, 2016 ( https://clinicaltrials.gov/ct2/show/NCT02807766 ).

Meta-analysis of the efficacy of digital therapies in children with attention-deficit hyperactivity disorder.

Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in childhood. The aim of this meta-analysis was to summarize the available evidence for the efficacy of digital therapeutics in children and adolescents with ADHD. Methods: We searched the MEDLINE, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews), and Web of Science (science and social science citation index) databases for relevant studies and used Stata 15.0 software to carry out the meta-analysis. Results: A total of 31 studies involving 2169 participants (1665 boys and 504 girls) aged 4-17 years old were included in the final analysis. The meta-analysis results showed that digital interventions improved the symptoms of inattention with an effect value of -0.20 (95% confidence interval [CI] -0.36, -0.04) and decreased the continuous performance task (CPT) reaction time (effect, -0.40, 95% CI -0.73, -0.07) in ADHD patients. The score for impulsive hyperactivity was slightly decreased (effect, -0.07, 95% CI -0.23, 0.09). Moreover, executive function was improved (effect, 0.71, 95% CI 0.37, 1.04). The capability of working memory appeared to be increased (effect, 0.48, 95% CI 0.21, 0.76) between the two groups. Visual appraisal of the sensitivity analysis suggested the absence of heterogeneity, and no obvious publication bias was detected. Discussion: Based on the existing literature evidence, we conclude that digital therapy can be a promising therapeutic strategy for ADHD patients.

Gut microbiome profiles may be related to atypical antipsychotic associated overweight in Asian children with psychiatric disorder: a preliminary study.

Objective: Atypical antipsychotics (APs) modify the gut microbiome, and weight gain in response to AP could be mediated by the gut microbiome. Thus, the present study aimed to explore the changes in the gut bacterial microbiome in AP-exposed children with obesity. Methods: To rule out the confounder of AP indication, the gut bacterial microbiome was compared between healthy controls (Con) and AP-exposed individuals with overweight (APO) or normal weight (APN). Fifty-seven AP-treated outpatients (21 APO and 36 APN) and 25 Con were included in this cross-sectional microbiota study. Results: AP users, regardless of body mass index, exhibited decreased microbial richness and diversity and a distinct metagenomic composition compared to the Con. Although no differences in the microbiota structure were observed between APO and APN groups, the APO group was characterised by a higher abundance of Megamonas and Lachnospira. Additionally, the differences in the microbial functions were observed between APO and APN groups. Conclusions: The gut bacterial microbiota of APO children revealed taxonomic and functional differences compared to Con and APN. Further studies are needed to verify these findings and to explore the temporal and causal relationships between these variables.

Altered gut bacterial-fungal interkingdom networks in children and adolescents with depression.

BACKGROUND: Most studies of the gut-brain axis have focused on bacteria; little is known about commensal fungi. Children and adolescents with depression were reported to have gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been evaluated. METHODS: Faecal samples were obtained from 145 children and adolescents with depression and 110 age- and gender-matched healthy controls. We analysed the fungal microbiota, including in terms of their associations with the gut microbiota, and subjected the internal transcribed spacer 2 (ITS2) rRNA gene to mitochondrial sequencing. RESULTS: Our findings revealed unaltered fungal diversity, but altered taxonomic composition, of the faecal fungal microbiota in the children and adolescents with depression. Key fungi such as Saccharomyces and Apiotrichum were enriched in the depressed patients, while Aspergillus and Xeromyces showed significantly decreased abundance. Interestingly, the bacterial-fungal interkingdom network was markedly altered in the children and adolescents with depression, and mycobiome profiles were associated with different bacterial microbiomes. LIMITATION: The cross-sectional design precluded the establishment of a causal relationship between the gut mycobiota and the children and adolescents with depression. CONCLUSIONS: The gut mycobiome is altered in the children and adolescents with depression. Our findings suggest that fungi play an important role in the balance of the gut microbiota and may help identify novel therapeutic targets for depression.

Gut microbiota is associated with weight gain in children treated with atypical antipsychotic: A pilot longitudinal study.

We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium_hallii_group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain.

Exposure to selective noradrenalin reuptake inhibitors during the first trimester of pregnancy and risk of congenital malformations: A meta-analysis of cohort studies.

Selective serotonin-noradrenalin reuptake inhibitors (SNRIs) are used to treat depression and anxiety during pregnancy; however, information regarding their foetal safety is limited. Cohort studies concerning congenital malformations in infants born to mothers exposed to SNRIs during the first trimester of pregnancy were identified. Eight studies were included in the analysis. In general, the use of SNRIs was not associated with an increased risk of overall congenital malformations when compared with no exposure (rate ratio [RR] = 1.07, 95% confidence interval [CI] = 0.94-1.22; P = 0.31), exposure to SSRIs (RR = 1.12, 95% CI = 0.97-1.31; P = 0.12) and no exposure with clinical indication (RR = 1.04, 95% CI = 0.9-1.2; P = 0.564). A significantly increased risk of cardiac malformations was observed (RR = 1.33, 95% CI = 1.15-1.53; P < 0.001); however, this association was not statistically significant when the reference group comprised mothers exposed to SSRIs (RR = 1.1, 95% CI = 0.85-1.43; P = 0.47) or no exposure with clinical indication (RR = 1.17, 95% CI = 0.95-1.42; P = 0.13). The evidence shows no increased risk of congenital malformations and argues against a substantial cardiac teratogenic effect of SNRIs.

Fecal microbiota in pediatric depression and its relation to bowel habits.

Although gut microbiota dysbiosis has been observed in the fecal samples of depressive adult patients, the detailed structure and composition of microbiota in pediatric depression remain unclear. To enhance our understanding of gut microbiota structure in depressive children, as well as the relationship between gut microbiota and bowel habits, we performed 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 171 children (101 depressive patients and 70 controls) aged 12-18 years. Further analysis consisting of 30 drug-naive patients and 23 controls was performed to validate the results. Compared to controls, we found markedly decreased microbial richness and diversity, a distinct metagenomic composition with reduced short-chain fatty acid-producing bacteria (associated with healthy status), and overgrowth of bacteria such as Escherichia-Shigella and Flavonifractor in pediatric depression. Further analyses limited to drug-naive patients found similar results. Notably, we also observed that several taxa may be involved in the pathogenesis of disordered bowel habits in pediatric depression. Our findings suggest could inform future pediatric depression interventions specifically targeting the bacteria associated with bowel movements.

Off-the-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma.

BACKGROUND: Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use of autologous CAR T cells necessitating the manufacture of individualized therapeutic products for each patient. To address this challenge, we have generated an off-the-shelf, allogeneic CAR T cell product for the treatment of glioblastoma (GBM), and present here the feasibility, safety, and therapeutic potential of this approach. METHODS: We generated for clinical use a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic T-lymphocyte (CTL) product genetically engineered using zinc finger nucleases (ZFNs) to permanently disrupt the glucocorticoid receptor (GR) (GRm13Z40-2) and endow resistance to glucocorticoid treatment. In a phase I safety and feasibility trial we evaluated these allogeneic GRm13Z40-2 T cells in combination with intracranial administration of recombinant human IL-2 (rhIL-2; aldesleukin) in six patients with unresectable recurrent GBM that were maintained on systemic dexamethasone (4-12 mg/day). RESULTS: The GRm13Z40-2 product displayed dexamethasone-resistant effector activity without evidence for in vitro alloreactivity. Intracranial administration of GRm13Z40-2 in four doses of 108 cells over a two-week period with aldesleukin (9 infusions ranging from 2500-5000 IU) was well tolerated, with indications of transient tumor reduction and/or tumor necrosis at the site of T cell infusion in four of the six treated research subjects. Antibody reactivity against GRm13Z40-2 cells was detected in the serum of only one of the four tested subjects. CONCLUSIONS: This first-in-human experience establishes a foundation for future adoptive therapy studies using off-the-shelf, zinc-finger modified, and/or glucocorticoid resistant CAR T cells.

Epidemiology of Childhood Trauma and Analysis of Influencing Factors in Psychiatric Disorders Among Chinese Adolescents: A Cross-sectional Study.

Childhood trauma (CT) can lead to long-term psychiatric disturbances. The current study investigated the prevalence of CT and its associated risk factors among Chinese adolescents with psychiatric disorders. Adolescents were recruited from a large study on mental health in the Hunan province of China in 2014. The study had a two-phase cross-sectional design. Patients with mental disorders (n = 907) and healthy subjects (n = 2,240) completed the Childhood Trauma Questionnaire-Short Form. Of all types of CT, emotional neglect (EN; 48.44%-68.82%) and physical neglect (PN; 60.0%-72.1%) were most common among adolescents. The experience of emotional abuse (EA), physical abuse (PA), sexual abuse (SA), EN, and multiple types of trauma (≥3) was higher among adolescents with psychiatric disorders than the healthy comparison group. Moreover, the results of logistic regression analysis showed that living in semi-urban areas and villages, having a sibling, and having bad-to-average academic performance were risk factors for CT among adolescents with psychiatric disorders (p < .05). In additional, the results of logistic regression analysis revealed that being a left-behind child and bad academic performance were risk factors for experiencing multiple types (≥3) of CT (p < .05), while being female and having siblings were found to be protective factors against (≥3) CT (p < .05). In summary, the prevalence rate of CT (especially multiple types of trauma) is high among adolescents with psychiatric disorders. These results indicate the importance of reducing CT to limit the likelihood of psychiatric disorders, especially among adolescents.

Early Life Antibiotic Exposure and the Subsequent Risk of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

This study was conducted to assess this association between early life antibiotic exposure and the risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in later life. The results showed that early life antibiotic exposure was associated with an increased risk of ASD (OR = 1.13, 95% confidence interval (CI): 1.07-1.21) or ADHD (OR = 1.18, 95% CI: 1.1-1.27). However, this association for ASD (OR = 1.04, 95% CI: 0.97-1.11) or ADHD (OR = 0.98, 95% CI: 0.94-1.02) disappeared when data from sibling-matched studies were pooled. The statistically significant association between early life antibiotic exposure and ASD or ADHD in later life can be partially explained by unmeasured genetic and familial confounding factors.

Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis.

Background: The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent. Methods: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk. Results: Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25-1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03-1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99-1.16, P = 0.076), implying that the association was due to confounding factors. Conclusion: The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding. Systematic Review Registration: Identifier CRD42022302892.

An Exploratory Cohort Study of the Association between the Level of Testosterone and Suicidal Ideation in Hospitalized Adolescent Females with Depression in China.

BACKGROUND: To date, around 4 per 100,000 adolescents committed suicide within the 29 OECD countries. The suicidal behavior is related to psychological factors, genetics, neurobiology, and other biomarkers. The aim of this study was to examine risk factors for the development of suicidal ideation in adolescent females with depression, focusing on the relationship between different testosterone levels and suicidal ideation, in order to help develop strategies to intervene in suicidal behavior in female adolescents with depression. METHOD: In this single-center prospective cohort study, we enrolled adolescent females with depression. We collected information on their baseline data, testosterone levels, symptom self-rating scale scores, suicidal ideation, non-suicidal self-injurious (NSSI) behaviours, and suicide attempts. We used multivariate logistic regression to identify risk factors for the development of suicidal ideation in adolescent females with depression. RESULTS: A total of 113 hospitalized adolescent females were enrolled with a mean age of 13.5 (1.20). Among these patients, there were 86 (76.11%) subjects who suffered from suicidal ideation, 59 (52.21%) had NSSI and 23 (20.35%) had suicide attempt behavior. In the final model, higher level of testosterone (p=0.04) and higher age (p=0.02) were associated with the higher odds of having suicidal ideation. CONCLUSION: In this exploratory cohort study, the emergence of suicidal ideation was common among adolescent females with depression. This study is consistent with the other studies. It shows that the age is a potential predictor for suicidal ideation in hospitalized adolescent females with depression.

Association of Attention Deficit/Hyperactivity Disorder With Events Occurring During Pregnancy and Perinatal Period.

Background: The relationship of events occurring during pregnancy and perinatal period with attention deficit/hyperactivity disorder (ADHD) is not clear. Thus, the focus of the current study was to examine the effects of events occurring during pregnancy and perinatal period on ADHD. Methods: A two-phase cross-sectional study was performed across 13 schools in Changsha and Yiyang cities from March to December, 2014. We preliminarily screened all students using CBCL and established the diagnosis using Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). A total of 3,418 questionnaires were effectively completed in this study. Results: History of threatened abortion (TA) [odds ratio (OR): 1.707 (1.201-2.426)] (vs. No-TA) and neonatal asphyxia (NA) [OR: 2.497(1.225-5.09)] (vs. health) showed a positive association with ADHD. On subgroup analysis, TA [OR: 2.216 (1.458-3.369)] (vs. No-TA) was a risk factor for ADHD without comorbidity; instrumental delivery [OR: 2.748 (1.057-7.142)] (vs. natural birth) and NA [OR: 2.789 (1.222-6.361)] (vs. health) were risk factors for ADHD in the subgroup of ADHD with comorbidity; TA (vs. no-TA) and NA (vs. health) were risk factors for ADHD among male students [ORs: 2.232 (1.439-3.462) and 2.808 (1.115-7.068), respectively], while low birth weight (LBW) (vs. normal birth weight) was a risk factor [OR: 2.054 (1.063-3.967)] for ADHD among female students. Conclusion: TA was a risk factor for ADHD in the absence of comorbid conditions; instrumental delivery and NA were risk factors for ADHD in the subgroup of ADHD with comorbidity; TA and NA were risk factors for ADHD among male students. LBW was a risk factor for ADHD among female students.

Adjuvant psychotherapy in early-stage bipolar disorder: A protocol for systematic review and meta-analysis.

OBJECTIVE: There is no systematic review or meta-analysis to evaluate the efficacy of adjuvant psychotherapy in early-stage bipolar disorder. Therefore, the goal of this meta-analysis is to examine the evidence supporting psychotherapy as an efficacious approach to treating bipolar disorder. METHODS: Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library were searched in March 2021 by two independent reviewers. Data extraction was performed independently, and any conflict was resolved before final analysis. Only randomized clinical trials were included in this study. The trial entails 1 primary outcome measure (relapse) and several secondary outcome measures: time to relapse, relapse rate, days missed at work/school (record, interview), and social functioning level. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: We hypothesized that combined psychotherapy and pharmacological interventions would be superior to pharmacological interventions alone regarding the time to relapse into a manic or depressive episode. CONCLUSION: This study expects to provide credible and scientific clinical evidence for the efficacy and safety of combined psychotherapy and pharmacological interventions in the treatment of bipolar disorder. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/ZGS6W.

Maternal infection exposure and the risk of psychosis in the offspring: A systematic review and meta-analysis.

The relationship between maternal infection exposure and the risk of psychosis in the offspring is inconsistent. We systematically assessed this relationship. Unrestricted searches of the PubMed and Embase databases were conducted, with an end date of February 1, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Twenty-three observational studies were included in the analysis. The results showed that mothers who had a history of infection during pregnancy experienced a significantly increased risk of developing psychosis in offspring (OR = 1.25, 95% confidence interval (CI): 1.1-1.41; P = 0.001). Sensitivity and subgroup analyses yielded consistent results. For specific pathogens, the risk of developing psychosis in offspring was increased among mothers with herpes simplex virus 2 (HSV-2) exposure (OR, 1.32; 95% CI, 1.09-1.6; P = 0.004). However, other maternal-specific pathogen exposures were not significantly associated with the risk of psychosis in offspring. No evidence of publication bias was observed. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal infection exposure may be associated with a greater risk of psychosis in the offspring.

Altered gut bacterial-fungal interkingdom networks in patients with current depressive episode.

INTRODUCTION: Bacterial dysbiosis has been described in patients with current depressive episode (CDE); however, the fungal composition in the gut has not been investigated in these patients. METHODS: Here, we characterized the fungal gut mycobiota in patients with CDE. We systematically characterized the microbiota and mycobiota in fecal samples obtained from 24 patients with CDE and 16 healthy controls (HC) using 16S rRNA gene- and ITS1-based DNA sequencing, respectively. RESULTS: In patients with CDE, bacterial dysbiosis was characterized by an altered composition and reduced correlation network density, and the gut mycobiota was characterized by a relative reduction in alpha diversity and altered composition. Most notably, the CDE group had higher levels of Candida and lower level of Penicillium than the HC group. Compared with the HC group, the gut microbiota in patients with CDE displayed a significant disruption in the bacteria-fungi correlation network suggestive of altered interkingdom interactions. Furthermore, a gut microbial index based on the combination of eight genera (four bacterial and four fungal CDE-associated genera) distinguished CDE patients from controls with an area under the curve of approximately 0.84, suggesting that the gut microbiome signature is a promising tool for disease classification. CONCLUSIONS: Our findings suggest that both bacteria and fungi contribute to gut dysbiosis in patients with CDE. Future studies involving larger cohorts and metagenomic or metabolomic analyses may clarify the structure and potential roles and functions of the gut mycobiome and its impact on the development of CDE.

Meta-analysis found that studies may have overestimated Caesarean section risks for attention-deficit hyperactivity disorder by ignoring confounding factors.

AIM: Epidemiological studies on associations between Caesarean sections (C-sections) and attention-deficit hyperactivity disorder (ADHD) have been inconsistent, and we performed a meta-analysis. METHODS: We systematically searched PubMed and Embase to December 2018 and included nine hospital-based and population registry studies published in 2011-2018. These covered a total study cohort of more than 2.5 million people in eight countries: Australia, Brazil, Denmark, Finland, Germany, Sweden, Turkey and the UK. The analysis provided summary odds ratios (ORs) and 95% confidence intervals (CI) while taking heterogeneity into account. RESULTS: We found that that C-sections were associated with a small increase in the risk of ADHD (OR 1.14, 95% CI 1.11, 1.17, I2 0%) in offspring. In subgroup analyses, the association remained for both infants born after elective C-sections (OR, 1.15, 1.11, 1.19, I2 0%) and emergency C-sections (OR, 1.13, 1.1, 1.17, I2 45.4%). However, these were only marginally significant when we pooled data from siblings from other pregnancies (OR, 1.06, 1.00-1.13, I2 0%), implying that the association was due to confounding. CONCLUSION: The statistically significant association between C-sections and ADHD in children can be partially explained by unmeasured confounding. Further research controlling for important confounders is required before firm conclusions can be drawn.

Analysis of gut mycobiota in first-episode, drug-naïve Chinese patients with schizophrenia: A pilot study.

BACKGROUND: Accumulating evidence has focused on elucidating the bacterial component of the gut microbiota in patients with schizophrenia (SC); however, the fungal composition in the gut has not been investigated, although previous studies have suggested that gut mycobiota may be intricately linked to this disorder. The purpose of this analysis was to examine gut bacterial and fungi in first-episode, drug- naïve adult SC patients in relation to age- and sex-matched healthy controls (HC). METHODS: Ten SC patients and 16 HCs were enrolled in this cross-sectional study, and their gut microbiota and mycobiota were systematically characterized using 16S rRNA gene- and ITS1-based DNA sequencing. RESULTS: The microbiota of the SC patients were characterized by increased abundance of harmful bacterial (Proteobacteria) and decreased short-chain fatty acid (SCFA)-producing bacteria, such as the Faecalibacterium and Lachnospiraceae genera. The gut mycobiota were characterized by a relative reduction in alpha diversity and altered composition. Most notably, the SC group had a higher level of Chaetomium and a lower level of Trichoderma than the HC group. Furthermore, the gut microbiota in patients with SC displayed a significant enhancement in the bacteria-fungi correlation network, suggestive of altered interkingdom interactions. CONCLUSIONS: Both the bacterial gut microbiota as well as the gut mycobiota contributed to gut dysbiosis in patients with SC. However, our study was limited by sample size, and additional studies involving larger cohorts characterizing the gut mycobiome in SC patients are needed to form a foundation for research into the relationship between mycobiota, dysbiosis, and SC development.