Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

Schizophrenia (SCZ) is a complex disorder characterized by acute symptom exacerbations. Amisulpride, an antipsychotic, has shown effects beyond its primary neurochemical actions, suggesting an influence on the gut microbiome, cytokine modulation, and short-chain fatty acid (SCFA) metabolism. This study aims to investigate these broader effects by examining changes in serum SCFA levels and gene expression profiles in peripheral blood mononuclear cells (PBMCs) following amisulpride treatment. Patients with SCZ undergoing a four-week amisulpride regimen were enrolled. Serum SCFA levels were quantified by gas chromatography, and gene expression profiling was performed in PBMCs using real-time quantitative polymerase chain reaction to assess treatment-associated changes. Results revealed that treatment with amisulpride resulted in a significant increase in serum acetate levels. Gene expression analysis revealed upregulation of G-protein coupled receptor 109a (GPR109a), histone deacetylase 1 (HDAC1), G-protein coupled receptor 43 (GPR43), Toll-like receptor 2 (TLR2), soluble CD14 (sCD14), and N-methyl-d-aspartate receptor (NMDAR), while Toll-like receptor 4 (TLR4) and pregnane X receptor (PXR) were downregulated. These findings suggest that amisulpride may modulate acetate metabolism and immune signaling pathways in SCZ, potentially contributing to anti-inflammatory effects and neuroimmune regulation. The observed increase in acetate, a key microbial metabolite, and the altered expression of immune-related genes suggest a possible link between metabolic shifts and immunomodulatory responses in SCZ pathophysiology. However, direct evidence linking these changes to gut-brain axis mechanisms remains insufficient. Further research is needed to elucidate the therapeutic implications of these metabolic and immunological alterations and their potential role in symptom modulation.

Abdominal low-intensity pulsed ultrasound (LIPUS) stimulation has potential as a novel therapeutic strategy against neuroinflammation via inhibition of inflammatory responses in the colon. This study aimed to evaluate whether abdominal LIPUS could alleviate MK-801-induced schizophrenia-like negative symptoms through gut-brain communication.

Rats administered with MK-801 were treated daily for 5 days with either LIPUS or Lactobacillus plantarum PS128, while another group of MK-801-administered rats received no treatment. Following LIPUS or PS128 treatment, rats underwent behavioral testing, western blot analysis, and histological examination. Changes in the gut bacteria composition were examined through 16S rRNA sequencing analysis.

MK-801 administration reduced NMDAR1 and VGAT expression in the medial prefrontal cortex (mPFC) of rats, leading to an imbalance in the excitation/inhibition (E/I) ratio. It also decreased 5-HT1AR and 5-HT2AR density, resulting in reduced concentrations of dopamine and serotonin (5-HT). This induced prepulse inhibition, anhedonia, and social withdrawal behaviors, accompanied by a reduction in gut microbiota diversity. Abdominal LIPUS stimulation effectively lessened the MK-801-induced reduction in gut microbiota diversity, restored NMDAR1, 5-HT1AR, and 5-HT2AR density, enhanced dopaminergic neuron activity, and increased dopamine and 5-HT release in the mPFC, thereby reversing behavioral abnormalities.

These results suggest that abdominal LIPUS alleviates MK-801-induced schizophrenia-like negative symptoms by modulating serotonin signaling and the gut microbiota.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder with unclear pathogenesis, limiting advances in early diagnosis and targeted interventions. Increasing evidence suggests that the gut microbiome contributed to SCZ pathophysiology, yet comprehensive characterization across illness stages remains lacking. This meta-analysis aimed to characterize gut microbial alterations across the SCZ spectrum disorder, including individuals at ultra-high risk for psychosis, first-episode psychosis (FEP) and chronic SCZ patients. A systematic search of 10 databases identified 91 case-control studies. Gut microbial outcome measures included relative abundance, alpha and beta diversity. Review Manager and R were used to analyze the data. The results showed that patients with SCZ exhibited significantly reduced alpha diversity, particularly in Shannon, Chao1, Observe and Evenness indices, compared to healthy controls. Beta diversity also differed significantly, with 88.5 % of studies reporting distinct microbial profiles across SCZ stages. Quantitative analysis revealed significantly increased relative abundance of Bacteroides and a decrease abundance of Bifidobacterium and Lactobacilli in FEP patients compared to healthy controls. Qualitative analysis further showed increasing abundance in Lactobacillus, Prevotella and Collinsella, but decreasing abundance in Faecalibacterium, Butyricicoccus, and Blautia in SCZ. Bifidobacterium exhibited stage-specific changes, decreasing in first-episode psychosis but increasing in chronic stages, while Bacteroides followed an opposite trajectory. Notably, Lactobacillus demonstrated an early upward tractor in high-risk individuals, persisting to chronic stages. This meta-analysis identified dynamic and consistent alterations in the gut microbial across the SCZ spectrum. These findings implicated the potentials of gut microbes as early indicators for identification and intervention of SCZ.

Tourette syndrome (TS) is a common chronic neuropsychiatric disorder with a prevalence of approximately 1% in children and adolescents. TS is characterized by sudden involuntary motor tics along with vocal tics. A pathological study on postmortem patients has reported a 50-60% reduction in striatal gamma-aminobutyric acidergic (GABAergic) interneurons, suggesting a role for GABAergic system imbalances in tic disorder development. However, the effect of exogenous GABA administration on tic alleviation remains unreported.

In this study, we aim to investigate the therapeutic effects of exogenous GABA on TS-like behaviors in Sprague-Dawley rats and explore its potential mechanisms, including gut microbiota regulation, oxidative stress mitigation, and restoration of GABA-glutamate balance, to provide insights into TS pathogenesis and alternative treatment strategies.

A TS model rat was established through intraperitoneal administration of 3,3-Iminodipropionitrile (150 mg/kg/day), followed by GABA (20 mg/kg/day) administration by gavage. 15 minutes of behavioral testing (stereotypical behavior and head twitching behavior) was then conducted. 16S rRNA sequencing identified microbiome changes, and LC-MS assessed striatal metabolite changes.

The results showed that a 4-week GABA treatment alleviated TS-like behavior in rats. GABA treatment led to an increase in Acinetobacter and other beneficial bacteria. GABA also significantly upregulated 15 striatal metabolites compared with TS group. By correlation analysis of striatal metabolites and intestinal bacteria, statistical analysis showed that Clostridium_sensu_stricto_1 was negatively correlated with metabolites on the top 20 differential gut microbiota and metabolites. Moreover, changes in gut microbiota correlated with alterations in striatal metabolites, suggesting a gut-brain axis involvement.

Exogenous GABA alleviated TS-like behavior in rats by reducing harmful gut flora and modulating striatal GABA-glutamate metabolism. Despite challenges like low blood-brain barrier permeability and dose safety in humans, GABA's therapeutic potential may be realized through prodrug development and optimized dosing. These findings are preliminary and require further clinical validation.

Psychiatric disorders pose substantial global burdens on public health, yet therapeutic options remain limited. Recently, gut microbiota is in the spotlight of new research on psychiatric disorders, as emerging discoveries have highlighted the importance of gut microbiome in the regulation of central nervous system via mediating the gut-brain-axis bidirectional communication. While metagenomics studies have accumulated for psychiatric disorders, few systematic efforts were dedicated to integrating these high-throughput data across diverse phenotypes, interventions, geographical regions, and biological species. To present a panoramic view of global data and provide a comprehensive resource for investigating the gut microbiota dysbiosis in psychiatric disorders, we developed the PsycGM, a manually curated and well-annotated database that provides the literature-supported associations between gut microbiota and psychiatric disorders or intervention measures. In total, PsycGM incorporated 559 studies from 31 countries worldwide, encompassing research involving humans, rats, mice, and non-human primates. PsycGM documented 8907 curated associations between 1514 gut microbial taxa and 11 psychiatric disorders, as well as 4050 associations between 869 taxa and 232 microbiota-based and non-microbiota-based interventions. Moreover, PsycGM provided a user-friendly web interface with comprehensive information, enabling browsing, retrieving and downloading of all entries. In the application of PsycGM, we panoramically depicted the intestinal microecological imbalance in depression. Additionally, we identified 9 microbial taxa consistently altered in patients with depression, with the most common dysregulations observed for Parabacteroides, Alistipes, and Faecalibacterium; in animal models of depression, consistent changes were observed in 21 microbial taxa, most frequently reported as Helicobacter, Lactobacillus, Roseburia, and the ratio of Firmicutes/Bacteroidetes. PsycGM is a comprehensive resource for future investigations on the role of gut microbiota in mental and brain health, and for therapeutic target innovations based on modifications of gut microbiota. PsycGM is freely accessed at http://psycgmomics.info .

Gut microbiome is implicated in the onset and progression of major depressive disorder (MDD), but the dynamic alterations of depressive symptoms, gut microbiome, and fecal metabolome across different stages of stress exposure remain unclear. Here, we modified the chronic social defeat stress (CSDS) model to evaluate mice subjected to social defeat stress for 1, 4, 7, and 10 days. Behavioral tests, 16S rRNA, metagenomics, and fecal metabolomics were conducted to investigate the impact of stress exposure on behaviors, gut microbiota and fecal metabolites. We observed that depressive-like behaviors, such as anhedonia and social avoidance, worsened significantly as stress exposure increased. The microbial composition, function, and fecal metabolites exhibited distinct separations across the different social defeat stress groups. Mediation analysis identified key bacteria, such as Lachnospiraceae_UCG-001 and Bacteroidetes, and fecal metabolites like valeric acid and N-acetylaspartate. In our clinical depression cohort, we confirmed that fecal valeric acid levels, were significantly lower in depressive-like mice and MDD patients, correlating closely with stress exposure and anhedonia in mice. Further analysis of serum and brain metabolites in mice revealed sustained changes of N-acetylaspartate abundance in fecal, serum, and cortical samples following increasing stress exposure. Together, this study elucidated the characteristics of depressive-like behaviors, gut microbiome, and fecal metabolome across various social defeat stress exposure, and identified key bacteria and fecal metabolites potentially involved in modulating social defeat stress response and depressive-like behaviors, providing new insights into the pathogenesis and intervention of depression.

Although disturbances in the gut microbiome have been implicated in multiple sclerosis (MS), little is known about the changes and interactions between the gut microbiome and blood metabolome, and how these changes affect disease-modifying therapy (DMT) in preventing the progression of MS. In this study, the structure and composition of the gut microbiota were evaluated using 16S rRNA gene sequencing and an untargeted metabolomics approach was used to compare the serum metabolite profiles from patients with relapsing-remitting MS (RRMS) and healthy controls (HCs). Results indicated that RRMS was characterized by phase-dependent α-phylogenetic diversity and significant disturbances in serum glycerophospholipid metabolism. Notably, α-phylogenetic diversity was significantly decreased in RRMS patients during the chronic phase (CMS) compared with those in the acute phase (AMS). A distinctive combination of two elevated genera (Slackia, Lactobacillus) and five glycerophospholipid metabolism-associated metabolites (four increased: GPCho(22:5/20:3), PC(18:2(9Z,12Z)/16:0), PE(16:0/18:2(9Z,12Z)), PE(18:1(11Z)/18:2(9Z,12Z)); one decreased: PS(15:0/22:1(13Z))) in RRMS patients when comparing to HCs. Moreover, a biomarker panel consisting of four microbial genera (three decreased: Lysinibacillus, Parabacteroides, UBA1819; one increased: Lachnoanaerobaculum) and two glycerophospholipid metabolism-associated metabolites (one increased: PE(P-16:0/22:6); one decreased: CL(i-12:0/i-16:0/i-17:0/i-12:0)) effectively discriminated CMS patients from AMS patients, which indicate correlation with higher disability. Additionally, DMTs appeared to attenuate MS progression by reducing UBA1819 and upregulating CL(i-12:0/i-16:0/i-17:0/i-12:0). These findings expand our understanding of the microbiome and metabolome roles in RRMS and may contribute to identifying novel diagnostic biomarkers and promising therapeutic targets.

Introduction. Depression has become one of the mental diseases that seriously affect human health. Its mechanism is very complex, and many factors influence the condition. An imbalance of the gut microbiota is being considered as a factor that impacts the occurrence and progression of depression. Future therapies may therefore tap into this connection, treating depression through manipulation of the gut microbiome.Hypothesis/Gap Statement. Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin from Latrodectus tredecimguttatus eggs, was previously demonstrated to inhibit excessive inflammation and improve depression behaviours, suggesting that it might be able to regulate the balance of gut microbiota. The aim of this study was to explore the effects of LPS and LETX-VI on depressive behaviours and gut microbiota and to analyse correlations between changes in the gut microbiota and depressive behaviours.Methodology. A murine model of depression was established, and the effects of LPS and LETX-VI treatment on depressive behaviours and gut microbiota were investigated.Results. In the murine model, depressive behaviour was induced by LPS; the ratio of Firmicutes to Bacteroidetes (F/B) and the number of pro-inflammatory bacteria in the gut microbiota increased (P<0.01), while butyric acid-producing bacteria with anti-inflammatory effect decreased (P<0.05). Furthermore, the metabolic function of the gut microbiota was disrupted, and the level of virulence factors among gut microbiota was up-regulated (P<0.05). Association analysis showed that the changes in the composition and function of gut microbiota were closely related to the depression phenotype of mice, suggesting that the abnormal function of gut microbiota is linked to depression. However, when LETX-VI was applied before LPS injection, the LPS-induced changes in the gut microbiota were alleviated, and the depressive behaviour greatly improved.Conclusion. LETX-VI can prevent depressive behaviour by regulating the composition and/or function of the gut microbiota.

The oral microbiota is associated with neuro-psychiatric disorders. However, there is presently inadequate comprehension regarding the correlation between schizophrenia and the oral microbiota. Moreover, patients with schizophrenia frequently exhibit poor oral health, potentially influencing research outcomes. Therefore, this study aims to investigate changes in the oral microbiota and oral health status in drug-free schizophrenia patients.

Oral microbiota samples were collected from 50 drug-free patients with schizophrenia and 50 healthy controls (HCs). The downstream microbiota analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16 S rRNA gene.

The alpha diversity of SCZ group is increased, such as the Shannon index (p < 0.001) and Simpson index (p = 0.004), while the community structure also displays variance compared to the HC group (p < 0.001). Key discriminative taxa were found in LEfSe analysis, including the phyla Fusobacteriota, Firmicutes, and Actinobacteriota. The differential taxa and microbial functions showed a strong correlation with clinical oral conditions. Further analysis demonstrated that models based on the entire oral microbiota effectively distinguished SCZ patients from HC (AUC = 0.97).

The significant changes in the microbiota of Drug-free SCZ patients appear to be closely associated with the poor oral environment.

Liver fibrosis, a complex process resulting from most chronic liver diseases, remains devoid of effective treatments. An increasing body of evidence links liver fibrosis to the "gut-liver axis", with disruptions in the gut microbiota-host balance emerging as a critical contributor to its progression. Cinnamaldehyde (Cin), a natural compound with antioxidant, anti-inflammatory, and anticytotoxic properties, has shown potential in counteracting hepatic stellate cell (HSC) activation. Additionally, Cin has been shown to promote probiotics in the intestine, thereby restoring a healthy microbial community. These characteristics position Cin as a promising candidate for liver fibrosis treatment through modulation of the gut-liver axis. In this study, a Vitamin A (Va)-formulated Cin Nanoemulsion (Va-Cin@NM) was developed to enhance the physicochemical stability of Cin while preserving intestinal homeostasis and facilitating targeted liver deposition. In bile duct ligation (BDL)-induced liver fibrosis in rats, Va-Cin@NM intervention significantly reduced bile duct-like structure proliferation and collagen deposition in the liver. These effects are likely attributed to the restoration of gut microbiota, increased short-chain fatty acid (SCFA) concentrations, and improved intestinal integrity. Moreover, Va-Cin@NM treatment suppressed harmful bacterial populations in the liver, thus mitigating immune injury and inflammatory cell recruitment. Consequently, oxidative stress and HSC activation were attenuated. Overall, Va-Cin@NM demonstrates significant potential as a nanotherapeutic approach for liver fibrosis by modulating the gut-liver axis.

Schizophrenia (SCZ) is a chronic and severe mental disorder with a complex molecular aetiology. Emerging evidence indicates a potential association between the gut microbiome and the development of SCZ. Considering the under-representation of African populations in SCZ research, this study aimed to explore the association between the gut microbiome and SCZ within a South African cohort. Gut microbial DNA was obtained from 89 participants (n = 41 SCZ cases; n = 48 controls) and underwent 16S rRNA (V4) sequencing. Data preparation and taxa classification were performed with the DADA2 pipeline in R studio followed by diversity analysis using QIIME2. Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC) was utilised to identify differentially abundant taxa. No statistically significant differences were observed between SCZ patients and controls in terms of alpha-diversity (Shannon q = 0.09; Simpson q = 0.174) or beta-diversity (p = 0.547). Five taxa, namely Prevotella (p = 0.037), Faecalibacterium (p = 0.032), Phascolarctobacterium (p = 0.002), Dialister (p = 0.043), and SMB53 (p = 0.012), were differentially abundant in cases compared to controls, but this observation did not survive correction for multiple testing. This exploratory study suggests a potential association between the relative abundance of Prevotella, Faecalibacterium, Phascolarctobacterium, Dialister, and SMB53 with SCZ case-control status. Given the lack of significance after correcting for multiple testing, these results should be interpreted with caution. Mechanistic studies in larger samples are warranted to confirm these findings and better understand the association between the gut microbiome and SCZ.

Chronic ketamine administration causes cognitive impairments similar to those observed in schizophrenia. Growing evidence suggests that patients with schizophrenia show alterations in gut microbiota, which is associated with cognitive impairments. Inulin could regulate gut microbiota. However, it is unclear whether chronic ketamine exposure causes cognitive impairments by mediating gut microbiota and whether inulin ameliorates these impairments. In this study, we found that chronic ketamine exposure for 14 days induced gut dysbiosis, thereby increasing gut permeability, upregulating LPS-activated TLR4-NF-κB-NLRP3 inflammatory pathway, causing hippocampal neuroinflammation and neuronal damage, activating tryptophan (TRP)-kynurenine (KYN)-kynurenic acid (KYNA) pathway in the hippocampus, peripheral serum, and feces, and thus leading to deficits in recognition memory and prepulse inhibition (PPI). In addition, inulin treatment restored gut dysbiosis by increasing the abundance of Turicibacter and Ileibacterium and decreasing the abundance of Alistipes, Alloprevotella, Desulfovibrio, and Parasutterella, which may improve gut barrier damage by upregulating tight junction protein expression, suppress LPS-mediated TLR4-NF-κB-NLRP3 inflammatory pathway to reduce neuroinflammation and neuronal damage, inhibit TRP-KYN-KYNA metabolism pathway, and thus alleviate chronic ketamine-associated impairments in PPI and memory. Our findings provide additional evidence that inulin treatment is a potential intervention strategy for treating chronic ketamine-associated cognitive impairments and cognitive deficits in schizophrenia.

Schizophrenia (SZ) is a chronic, severe mental disorder that presents significant challenges to diagnosis and effective treatment. Emerging evidence suggests that gut microbiota may play a role in the disease's pathogenesis. However, fewer studies have directly investigated the potential links between oral microbiota and SZ.

This study aimed to explore the relationship between salivary microbiota dysbiosis and SZ, examining microbial and metabolic alterations that may contribute to SZ pathophysiology.

Salivary samples from 30 hospitalized patients diagnosed with SZ and 10 healthy controls were collected. The microbial and metabolic profiles were analyzed using 16S rRNA gene sequencing and metabolomic profiling. Clinical parameters, including oral health status, were also evaluated to minimize variability in sampling.

Patients with SZ exhibited significantly poorer oral health compared to healthy controls, with more missing teeth and worse periodontal status. Microbiota sequencing revealed notable alterations in the overall structure and composition of the salivary microbiome in SZ patients, characterized by increased abundance of specific genera such as Neisseria and Porphyromonas. Metabolomic analysis indicated significant differences between the SZ and control groups, with upregulation of key metabolic pathways, including "β-alanine metabolism" and "vitamin digestion and absorption". Correlations between microbial dysbiosis and elevated levels of certain metabolites, such as L-methionine sulfoxide (L-MetO) and tyramine, were observed, suggesting links to oxidative stress.

The study highlights the presence of significant dysbiosis and metabolic dysfunction in the salivary microbiota of SZ patients, suggesting that alterations in the oral microbiome may contribute to SZ pathogenesis. These results provide new insights into potential diagnostic biomarkers and therapeutic targets for SZ. Further studies with larger sample sizes are required to validate these findings.

Fuzi-Lizhong pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms.

We aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms.

The active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model.

Network pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment.

These results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression.

Oropharyngeal microbiota may be implicated in the onset and progression of psychotic disorders. This scoping review aims to map the existing evidence concerning the composition, diversity, and metabolic pathways of the oropharyngeal microbiota in patients aged 18 to 65 with a main diagnosis of a psychotic disorder, including individuals at clinical high-risk for psychosis (CHRP) or experiencing first episode psychosis (FEP).

The scoping review was performed according to the PRISMA-ScR checklist. The systematic literature search was conducted using PubMed, Web of Science, and CINAHL until February 2024.

Seven cross-sectional studies were included, comprising 43 individuals at CHRP, 13 with FEP, 85 with first-episode of schizophrenia (FES), 171 with schizophrenia, and 8 with another schizophrenia spectrum disorder. The oropharyngeal microbiota showed an increase in Lactobacillus gasseri abundance in schizophrenia, and in Firmicutes/Proteobacteria phylum ratio in patients experiencing CHR-P and FES. In schizophrenia, an altered β-diversity was observed alongside increased metabolic pathways related to metabolite transporters. In FES, higher α-diversity and disruptions in amino acid, carbohydrate, and xenobiotic metabolism pathways were found. Hydrogen sulfide (H2S)-producing bacteria were generally enriched in all the stages of disease. Correlations were observed between oropharyngeal microbiota and psychotic symptom domains.

Potential microbial signatures, such as Lactobacillus gasseri and H2S-producing bacteria, were identified in the oropharyngeal microbiota. Alterations in the oropharyngeal microbiota composition and function may be associated with different stages of psychotic disorders, with some overlap between CHR-P and FES.

Schizophrenia is one of the most severe and chronic psychiatric disorders. Over the years, numerous treatment options have been introduced for schizophrenia. Although they are relatively successful in managing the positive symptoms of schizophrenia, most of the current treatments have a negligible effect on the negative and cognitive symptoms. Thus, none of them could prevent the relapse of psychotic episodes. Among the numerous hypotheses explaining the development and progression of schizophrenia, the cytokine hypothesis explains the role of inflammatory markers as a significant culprit in the development of schizophrenia. Elevated cytokines are reported in animal models and schizophrenic patients. The cytokine hypothesis is based on how increased inflammatory markers can cause changes in the dopaminergic, glutamate, and tryptophan metabolism pathways, like that observed in schizophrenic patients. Reasons, such as autoimmune disease, maternal immune activation, infection, etc., can pave the way for the development of schizophrenia and are associated with the negative, positive and cognitive symptoms of schizophrenia. Thus, there is a need to focus on the significance of anti-inflammatory drugs against these symptoms. The development of new treatment strategies in the management of schizophrenia can provide better therapeutic outcomes in terms of the severity of symptoms and treatment of drug-resistant schizophrenia. This review attempts to explain the association between elevated inflammatory markers and various neurotransmitters, and the possible use of medications like nonsteroidal anti-inflammatory drugs, monoclonal antibodies, statins, and estrogens as adjuvant therapy. Over the years, these hypotheses have been the basis for drug discovery for the treatment of schizophrenia.

Rising studies have consistently reported gut bacteriome alterations in schizophrenia (SCZ). However, little is known about the role of the gut virome on shaping the gut bacteriome in SCZ. Here in, we sequenced the fecal virome, bacteriome, and host peripheral metabolome in 49 SCZ patients and 49 health controls (HCs). We compared the gut bacterial community composition and specific abundant bacteria in SCZ patients and HCs. Specific gut viruses and host peripheral metabolites co-occurring with differential bacteria were identified using Multiple Co-inertia Analysis (MCIA). Additionally, we construct a latent serial mediation model (SMM) to investigate the effect of the gut virome on SCZ through the bacteriome and host metabolic profile. SCZ patients exhibited a decreased gut bacterial β-diversity compared to HCs, with seven differentially abundant bacteria, including Coprobacillaceae, Enterococcaceae etc. Gut viruses including Suoliviridae and Rountreeviridae, co-occur with these SCZ-related bacteria. We found that the viral-bacterial transkingdom correlations observed in HCs were dramatically lost in SCZ. The altered correlations profile observed in SCZ may impact microbiota-derived peripheral metabolites enriched in the bile acids pathway, eicosanoids pathway, and others, contributing to host immune dysfunction and inflammation. The SMM model suggested potential causal chains between gut viruses and SCZ, indicating that the effect of gut virome on SCZ is significantly mediated by bacteriome and metabolites. In conclusion, these findings provide a comprehensive perspective on the role of gut microbiota in the pathogenesis of SCZ. They reveal that patients with schizophrenia harbor an abnormal virome-bacteriome ecology, shedding light on the potential development of microbial therapeutics.

Comorbidities between gastrointestinal diseases and psychiatric disorders have been widely reported, with the gut-brain axis implicated as a potential biological basis. Thus, dysbiosis may play an important role in the etiology of schizophrenia, which is barely detected. Triple-hit Wisket model rats exhibit various schizophrenia-like behavioral phenotypes. The present study aimed to compare the diversity and abundance of gut microbiota in Wisket model and control rats; furthermore, to correlate the microbial taxonomic profiles to indices of behavioral change. Tail-flick and Ambitus tests were used to assess acute heat pain sensitivity, and record exploration and locomotor activity along with motivation in young adult, control and Wisket model rats. Fecal microbiota composition was profiled by deep sequencing of bacterial 16S rRNA, and it was correlated to behavioral phenotype. Wisket rats exhibited significantly decreased pain sensitivity, lower locomotor activity and exploration, and impaired motivation compared with controls. No significant differences were observed in bacterial alpha diversity between the groups; however, clear differences in community structure were observed. Wisket rats showed decreases in several genera of Firmicutes and Saccharimonas, and increases in Bacteriodetes and Helicobacter phyla compared with controls. Correlation analysis revealed significant associations between the microbiota profile and the behavioral phenotype. This is the first demonstration that fecal microbiota composition is markedly altered in a triple-hit schizophrenia rat model, suggesting the contribution of the microbiota-gut-brain axis in the development of the schizophrenia-like behavioral phenotype. Thus targeting the gut microbiota may be a novel approach to treat such impairments.

For a long time, traditional medicine has acknowledged the gut's impact on general health. Contemporary science substantiates this association through investigations of the gut microbiota, the extensive community of microorganisms inhabiting our gastrointestinal system. These microscopic residents considerably improve digestive processes, nutritional absorption, immunological function, and pathogen defense. Nevertheless, a variety of gastrointestinal and extra-intestinal disorders can result from dysbiosis, an imbalance of the microbial composition of the gut microbiota. A groundbreaking discovery is the gut-brain axis, a complex communication network that links the enteric and central nervous system (CNS). This bidirectional communication allows the brain to influence gut activities and vice versa, impacting mental health and mood disorders like anxiety and depression. The gut microbiota can influence this communication by creating neurotransmitters and short-chain fatty acids, among other biochemical processes. These factors may affect our mental state, our ability to regulate our emotions, and the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to explore the complex interrelationships between the brain and the gut microbiota. We also conducted a thorough examination of the existing understanding in the area of how microbiota affects social behaviors, including emotions, stress responses, and cognitive functions. We also explored the potential of interventions that focus on the connection between the gut and the brain, such as using probiotics to treat diseases of the CNS. This research opens up new possibilities for addressing mental health and neurological conditions in an innovative manner.

Sleep deprivation is a prevalent issue in contemporary society, with significant ramifications for both physical and mental well-being. Emerging scientific evidence illuminates its intricate interplay with the gut-brain axis, a vital determinant of neurological function. Disruptions in sleep patterns disturb the delicate equilibrium of the gut microbiota, resulting in dysbiosis characterized by alterations in microbial composition and function. This dysbiosis contributes to the exacerbation of neurological disorders such as depression, anxiety, and cognitive decline through multifaceted mechanisms, including heightened neuroinflammation, disturbances in neurotransmitter signalling, and compromised integrity of the gut barrier. In response to these challenges, there is a burgeoning interest in therapeutic interventions aimed at restoring gut microbial balance and alleviating neurological symptoms precipitated by sleep deprivation. Probiotics, dietary modifications, and behavioural strategies represent promising avenues for modulating the gut microbiota and mitigating the adverse effects of sleep disturbances on neurological health. Moreover, the advent of personalized interventions guided by advanced omics technologies holds considerable potential for tailoring treatments to individualized needs and optimizing therapeutic outcomes. Interdisciplinary collaboration and concerted research efforts are imperative for elucidating the underlying mechanisms linking sleep, gut microbiota, and neurological function. Longitudinal studies, translational research endeavours, and advancements in technology are pivotal for unravelling the complex interplay between these intricate systems.

The aim of this study was to investigate the relationship between gut microbiota and major depressive disorder (MDD) and schizophrenia (SCZ) by comparing 36 inpatients with these conditions to 29 healthy controls (HC) matched for age, sex, and body mass index (BMI). Individuals with SCZ exhibited greater microbiota richness compared to HC (FDR P(Q)=0.028). Taxonomically, while no significant differences were observed between the microbiota of MDD and SCZ patients in a head-to-head comparison, both patient groups differed significantly when compared to HC. Interestingly, besides common patterns (such as a higher abundance of Erysipelotrichaceae UCG-003 and Streptococcus, and a lower abundance of Lachnospiraceae ND3007 group), unique patterns were exhibited only in MDD (with a higher abundance of Anaerostipes, Q=0.004) or SCZ (with a higher abundance of Sutterella, Q=0.001, and a lower abundance of Clostridium sensu stricto 1, Q=0.002). The Random Forest algorithm identified Ruminococcus torques group, Lachnospiraceae UCG-001, and Erysipelotrichaceae UCG-003 as highly discriminative features for both SCZ and MDD, while Suturella and Holdemania were unique features for SZC, and Lachnospiraceae genus CAG-56 and Anaerostipes for MDD. Additionally, between 50 % and 60 % of the differentially abundant taxa were found among the top 10 influential features in the RF models. In conclusion, while no significant differences were found between the microbiota of MDD and SCZ patients, distinct microbial patterns were found in each group when compared to HC. The study did not confirm universal microbial biomarkers reported in other studies but showed that the observed differences concern the bacteria associated with inflammation, the production of short chain fatty acids (SCFA), and the synthesis of metabolites linked to mental health (lactic acid, gamma-aminobutyric acid - GABA). The application of machine learning holds promise for further understanding the complex relationship between microbiota and these psychiatric disorders. The observed results should be treated with caution due to the limitations of this study (mainly sample size), therefore further researches under standardized environmental conditions with consistent analytical and bioinformatics approaches are warranted.

Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation. This article is part of the Special Issue on "Personality Disorders".

Gut microbiota and infectious diseases affect neurological disorders, brain development, and function. Compounds generated in the gastrointestinal system by gut microbiota and infectious pathogens may mediate gut-brain interactions, which may circulate throughout the body and spread to numerous organs, including the brain. Studies shown that gut bacteria and disease-causing organisms may pass molecular signals to the brain, affecting neurological function, neurodevelopment, and neurodegenerative diseases. This article discusses microorganism-producing metabolites with neuromodulator activity, signaling routes from microbial flora to the brain, and the potential direct effects of gut bacteria and infectious pathogens on brain cells. The review also considered the neurological aspects of infectious diseases. The infectious diseases affecting neurological functions and the disease modifications have been discussed thoroughly. Recent discoveries and unique insights in this perspective need further validation. Research on the complex molecular interactions between gut bacteria, infectious pathogens, and the CNS provides valuable insights into the pathogenesis of neurodegenerative, behavioral, and psychiatric illnesses. This study may provide insights into advanced drug discovery processes for neurological disorders by considering the influence of microbial communities inside the human body.

The microbiota that inhabits the gastrointestinal tract has been linked to various gastrointestinal and non-gastrointestinal disorders. Scientists have been studying how the bacteria in our intestines have an effect on our brain and nervous system. This connection is called the "microbiota-gut-brain axis". Given the capacity of probiotics, which are live non-pathogenic microorganisms, to reinstate the normal microbial population within the host and confer advantages, their potential impact has been subjected to scrutiny with regard to neurological and mental conditions. Material sourced for this review included peer-reviewed literature annotated in the PubMed, Web of Science, Scopus, and Google Scholar databases. The result has indicated the integration of probiotics into a child's diet to enhance the neuro-behavioral symptoms. Notwithstanding this, the current data set has been found to be insufficient and inconclusive. The potential utility of probiotics for the prevention or treatment of neurologic and mental disorders has become a subject of substantial interest.

Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.

Schizophrenia is a complex heterogenous disorder thought to be caused by interactions between genetic and environmental factors. The theories developed to explain the etiology of schizophrenia have focused largely on the dysfunction of neurotransmitters such as dopamine, serotonin and glutamate with their receptors, although research in the past several decades has indicated strongly that other factors are also involved and that the role of neuroglial cells in psychotic disorders including schizophrenia should be given more attention. Although glia were originally thought to be present in the brain only to support neurons in a physical, metabolic and nutritional capacity, it has become apparent that these cells have a variety of important physiological roles and that abnormalities in their function may make significant contributions to the symptoms of schizophrenia. In the present paper, we review the interactions of brain microglia, astrocytes and oligodendroglia with aspects such as transmitter dysregulation, neuro-inflammation, oxidative stress, synaptic function, the gut microbiome, myelination and the blood-brain barrier that appear to affect the cause, development and treatment of schizophrenia. We also review crosstalk between microglia, astrocytes and oligodendrocytes and the effects of antipsychotics on neuroglia. Problems associated with studies on specific biomarkers for glia in schizophrenia are discussed.

Schizophrenia is a complex mental disorder influenced by genetic and environmental factors, including dietary habits. Oxidative stress and inflammation play a crucial role in the pathophysiology of schizophrenia. Emerging research suggests that diet may affect schizophrenia through different biological mechanisms beyond oxidative stress and inflammation. In particular, epigenetic changes may alter the expression of genes related to neurodevelopment and neurotransmitter systems, while neuroplasticity plays a crucial role in brain adaptation and resilience to psychiatric disorders.

The literature search included the main available databases (Science Direct, PubMed and Google Scholar), considering the English language, and our screening was performed based on several words such as "schizophrenia", "diet", "nutrients", "obesity", "oxidative stress", "inflammation", "antioxidants" and "prenatal nutritional deficiency". The review focused specifically on studies examining the relevance of diet in schizophrenia, as well as prenatal nutritional deficiency, obesity, oxidative stress, and inflammation associated with this disorder.

Following a review of the literature, it was found that nutritional deficiencies, including lack of omega-3 fatty acids, vitamins D, and B, during the prenatal and postnatal periods can have a negative impact on neurodevelopment and increase the risk of schizophrenia. Patients with schizophrenia have imbalances in antioxidant enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and reduced levels of antioxidants (vitamin E, vitamin C). These biochemical changes lead to an increase in markers of oxidative stress, including malondialdehyde (MDA). In addition, cytokine-mediated inflammation, microglial activation, and intestinal dysbiosis are associated with the onset of schizophrenia and the severity of schizophrenia symptoms. Currently, there is no universally accepted dietary regimen for control. However, various diets and nutritional methods are being researched and applied to alleviate the symptoms of schizophrenia and improve the overall health of patients, including the Mediterranean diet, the ketogenic diet, the gluten-free diet, and the DASH (Dietary Approaches to Stop Hypertension) diet.

A healthy diet, rich in anti-inflammatory nutrients and antioxidants, may help manage schizophrenia by reducing oxidative stress, preventing complications, and improving quality of life. Omega-3 fatty acids, vitamin D, and B vitamins are particularly important for brain development and function. In this review, we aim to analyze the literature on the influence of diet on schizophrenia, focusing on the role of prenatal nutritional deficiencies, obesity, oxidative stress, and inflammation.

Indoor fine particulate matter (PM2.5) poses a considerable hazard to the aging process, particularly in vulnerable populations such as schizophrenia patients who frequently spend extended periods in indoor environments. Currently, the evidence on which PM2.5 components contribute to accelerated aging remains unclear. To address these issues, we conducted a prospective, repeated-measurement study on 104 schizophrenia patients. Our findings indicated that exposure to PM2.5 components was significantly associated with accelerated biological aging in schizophrenia patients. Notably, the most prominent effects were observed for thallium (1.303, 95 % CI: 0.481-2.125), chromium (1.029, 95 % CI: 0.303-1.756), lead (1.021, 95 % CI: 0.296-1.746), antimony (0.915, 95 % CI: 0.233-1.597), selenium (0.854, 95 % CI: 0.209-1.499), and manganese (0.833, 95 % CI: 0.186-1.480). Multivariate analysis revealed that PM2.5 components predominantly induced alterations in serum glycerophospholipid metabolites, accelerating the aging process. This intricate connection was closely linked to the gut microbiota, particularly to species such as Dorea and Blautia. Mediation analysis showed that the Blautia-PC (16:0/0:0) pathway mediated the largest proportion (30.69 %) of the effect of manganese exposure on accelerating immune biological aging in schizophrenia patients, as measured using the Klemera-Doubal method. These results underscore the need to address pollution sources that harm health, and provide new evidence for improving regional air quality.

Antidepressants remain the first-line treatment for depression. However, the factors influencing medication response are still unclear. Accumulating evidence implicates an association between alterations in gut microbiota and antidepressant response. Therefore, the aim of this study is to investigate the role of the gut microbiota-brain axis in the treatment response of venlafaxine. After chronic social defeat stress and venlafaxine treatment, mice were divided into responders and non-responders groups. We compared the composition of gut microbiota using 16 S ribosomal RNA sequencing. Meanwhile, we quantified metabolomic alterations in serum and hippocampus, as well as hippocampal neurotransmitter levels using liquid chromatography-mass spectrometry. We found that the abundances of 29 amplicon sequence variants (ASVs) were significantly altered between the responders and non-responders groups. These ASVs belonged to 8 different families, particularly Muribaculaceae. Additionally, we identified 38 and 39 differential metabolites in serum and hippocampus between the responders and non-responders groups, respectively. Lipid, amino acid, and purine metabolisms were enriched in both serum and hippocampus. In hippocampus, the concentrations of tryptophan, phenylalanine, gamma-aminobutyric acid, glutamic acid, and glutamine were increased, while the level of succinic acid was decreased in the responders group, compared with the non-responders group. Our findings suggest that the gut microbiota may play a role in the antidepressant effect of venlafaxine by modulating metabolic processes in the central and peripheral tissues. This provides a novel microbial and metabolic framework for understanding the impact of the gut microbiota-brain axis on antidepressant response.

This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.

Twenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.

At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group.

Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.

There are some conflicting results regarding alterations of gut microbial composition in schizophrenia (SZ), even a few meta-analysis studies have addressed this field. Ignoring of antipsychotic medication effects may cause the large heterogeneity and impact on study results. This study is a meta-analysis to systematically evaluate composition of gut microbiota in patients with SZ, to elucidate the impact of antipsychotic use and reveal distinct and shared gut bacteria in SZ and antipsychotic medications. We re-analyzed the publicly available 16S rRNA-gene amplicon datasets by a standardized pipeline in QIIME2, used the natural log of response ratios as an effect index to directly and quantitatively compare composition of gut microbiota by random-effects meta-analysis with resampling tests in Metawin, ultimately to evaluate distinct abundance of gut bacteria. A total of 19 studies with 1968 participants (1067 patients with SZ and 901 healthy controls (HCs)) were included in this meta-analysis. The alterations of alpha diversity indices occurred in SZ on antipsychotics but not in drug-naïve or -free patients, while variation of beta diversity metrics appeared in SZ regardless of antipsychotic use. After antipsychotic treatment, reversed Simpson index, decreased observed species index and significant difference of Bray-Curtis distance were observed in patients. Especially, risperidone treatment increased the Shannon and Simpson indices. Noteworthy, three differed genera, including Lactobacillus, Roseburia and Dialister, were identified in both states of antipsychotic use. This meta-analysis is to provide a novel insight that SZ and antipsychotic medications present distinct and shared gut microbial composition.

The past decade witnessed substantial discoveries related to the psychosis spectrum. Many of these discoveries resulted from pursuits of objective and quantifiable biomarkers in tandem with the application of analytical tools such as machine learning. These approaches provided exciting new insights that significantly helped improve precision in diagnosis, prognosis, and treatment. This article provides an overview of how machine learning has been employed in recent biomarker discovery research in the psychosis spectrum, which includes schizophrenia, schizoaffective disorders, bipolar disorder with psychosis, first episode psychosis, and clinical high risk for psychosis. It highlights both human and animal model studies and explores a varying range of the most impactful biomarkers including cognition, neuroimaging, electrophysiology, and digital markers. We specifically highlight new applications and opportunities for machine learning to impact noninvasive symptom monitoring, prediction of future diagnosis and treatment outcomes, integration of new methods with traditional clinical research and practice, and personalized medicine approaches.

Neurological diseases are the primary cause of disability and death and impose substantial financial burdens. However, existing treatments only relieve symptoms and may cause many adverse effects. Natural products are a promising source of neurological therapeutic agents due to their excellent neuroprotective effect and safety. The gut microbiota has an essential impact on maintaining brain homeostasis via the gut-brain axis. Multiple investigations show that natural products offer neuroprotective effects by regulating gut microbiota-driven signaling networks.

This review aims to provide a systematic review of how natural products promote neurological health by harnessing the power of gut microbiota.

The pre-January 1, 2024 literature was gathered from several databases, including Scopus, PubMed, Google Scholar, and Web of Science, utilizing appropriate keywords. The gathered publications underwent a review process and were classified based on their study content, specifically focusing on the impact of natural products on gut microbiota and neurological health.

Here, we review how natural products promote neurological health by regulating the gut microbiota-brain axis. Specifically, we focus on the following areas. (1) Altering microorganism community structure, including increasing α-diversity and altering β-diversity. (2) Regulating the population of certain bacteria, including enriching beneficial microorganisms Akkermansia and Bifidobacterium, and inhibiting potentially hazardous microorganisms Bilophila, Klebsiella, and Helicobacter. (3) Regulating microbial neuroactive metabolites levels, including short-chain fatty acids, tryptophan and its derivatives, trimethylamine N-oxide, dopa/dopamine, γ-aminobutyric acid, and lipopolysaccharide. Furthermore, we review how natural products promote neurological health by regulating intestinal barrier homeostasis.

Natural products promote neurological health by harnessing the power of gut microbiota. This review will contribute to understanding how natural products promote neurological health by orchestrating the gut microbiota-brain axis.