The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.

JOURNAL/nrgr/04.03/01300535-202508000-00002/figure1/v/2024-09-30T120553Z/r/image-tiff Traumatic brain injury is a prevalent disorder of the central nervous system. In addition to primary brain parenchymal damage, the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury; however, the underlying pathogenesis remains unclear, and effective intervention methods are lacking. Intestinal dysfunction is a significant consequence of traumatic brain injury. Being the most densely innervated peripheral tissue in the body, the gut possesses multiple pathways for the establishment of a bidirectional "brain-gut axis" with the central nervous system. The gut harbors a vast microbial community, and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal, hormonal, and immune pathways. A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications. We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury, with a specific focus on the complex biological processes of peripheral nerves, immunity, and microbes triggered by traumatic brain injury, encompassing autonomic dysfunction, neuroendocrine disturbances, peripheral immunosuppression, increased intestinal barrier permeability, compromised responses of sensory nerves to microorganisms, and potential effector nuclei in the central nervous system influenced by gut microbiota. Additionally, we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury. This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the "brain-gut-microbiota axis."

The gut-brain axis is dysregulated as a consequence of alterations in the gut microbiota. These alterations increase toxic microbial metabolites, endotoxemia, and the release of immune mediators and contribute to the development of depression. Cubebin is a dibenzyl butyrolactone lignan, and its stem is also known as Agaru in Tibetan areas, it is commonly used as a sedative and tranquilizing medicine. This study aimed to investigate the effects of cubebin on chronic stress-induced depression-like behavior in mice. Cubebin was observed to mitigate depressive-like behavior in chronic unpredictable mild stress (CUMS) mice, influence the restoration of their cerebral cortex and hippocampal tissue morphology, and enhance the abundance of relevant intestinal flora in depression model mice, particularly by decreasing the abundance of Clostridium, Dorea, and Ruminococcus. The final protein function expression was normalized by regulating depression-related metabolic pathways. Concomitantly, the concentrations of neurotransmitters serotonin (5-HT), norepinephrine (NE), and dopamine (DA) in the brains of mice in the model group were enhanced, and their depressive symptoms were mitigated. Our study findings suggest that cubebin may ameliorate CUMS-induced depression in mice by modulating the microbe-gut-brain axis, elucidating the key effect of gut metabolites on depressive symptoms.

Despite advancements in immunotherapy, particularly regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 blockades, the clinical outcomes in non-small cell lung cancer (NSCLC) remain variable with limited predictive biomarkers currently available. The present study investigated respiratory microbiota diversity as a potential biomarker to predict the efficacy of PD-1 blockades in patients with advanced NSCLC. A retrospective analysis was conducted on 60 patients treated with PD-1 blockades from May 2019 to May 2023. Clinical data were collected and respiratory microbiota from deep induced sputum specimens were analyzed using 16S rRNA gene sequencing. An index of respiratory microbiota α diversity was applied and exploratory analysis was performed accordingly. The objective response rate (ORR) and disease control rate among the 60 patients receiving PD-1 blockades was 23.3% (95% CI, 13.4-36.0%) and 58.3% (95% CI, 44.9-70.9%), respectively. Analysis of prognostic data of patients with advanced NSCLC receiving PD-1 blockades monotherapy demonstrated a median progression-free survival of 3.4 months (95% CI, 2.54-4.26) and a median overall survival (OS) of 12.3 months (95% CI, 6.29-18.31). Patients were stratified into high and low α diversity groups based on the Shannon diversity index of respiratory microbiota. The ORR was increased in the high diversity group (26.7%) compared with that of the low diversity group (20.0%), although the difference was not statistically significant (P=0.542). Notably, the high diversity group demonstrated a longer median PFS (3.9 vs. 2.8 months; P=0.017) and median OS (16.8 vs. 6.8 months; P=0.016) compared with that of the low diversity group. These findings suggested that PD-1 blockades demonstrate promising therapeutic activity for patients with previously treated advanced NSCLC in clinical practice. Respiratory microbiota α diversity might serve as a potential biomarker to predict the efficacy of PD-1 blockades monotherapy in patients with advanced NSCLC in the future. Therefore, further prospective studies are warranted to validate these findings and to explore the underlying mechanisms by which respiratory microbiota might modulate the immune response to cancer therapy.

Emerging evidence supports gut microbiota's association with mental distress, particularly depression and anxiety, the microbiota-gut-brain axis was the believed to be the underlying mechanism. This study investigated the causal relationships between specific gut microbiota and depression and anxiety disorders using large-scale genome-wide association study (GWAS) data.

A two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal effects of 211 microbial taxa on depression and anxiety across three large GWAS databases: FinnGen, Pan-UKBB, and PGC. Sensitive analyses were followed to validate the robustness of results. Random-effect meta-analysis was further performed to enhance the statistical power.

The MR analysis revealed that the Bifidobacteriales (IVW: OR 0.90, 95 %CI 0.83 to 0.98) and Bifidobacteriaceae (IVW: OR 0.90, 95 %CI 0.83 to 0.98) had a protective effect against depression. Clostridiales (cML-MA: OR 0.88, 95 %CI 0.81 to 0.95) and Parasutterella (cML-MA: OR 0.75, 95 %CI 0.64 to 0.88) showed negative associations with depression. Increased abundance of Oxalobacteraceae (cML-MA: OR 1.78, 95 %CI 1.24 to 2.56), Deltaproteobacteria (cML-MA: OR 2.17, 95 %CI 1.38 to 3.40), and Desulfovibrionales (cML-MA: OR 2.22, 95 %CI 1.41 to 3.49) was associated with a higher risk of depression. For anxiety, protective effects were found for Actinobacteria (phylum: IVW: OR 0.83, 95 %CI 0.76 to 0.87; class: IVW: OR 0.84, 95 %CI 0.75 to 0.93), Bifidobacteriales (IVW: OR 0.80, 95 %CI 0.75 to 0.85), Bifidobacteriaceae (IVW: OR 0.80, 95 %CI 0.75 to 0.85) and Bifidobacterium [g] (IVW: OR 0.79, 95 %CI 0.74 to 0.84). Lactobacillaceae [f] (cML-MA: OR 1.18, 95 %CI 1.08 to 1.28), Clostridia [c] (cML-MA: OR 1.15, 95 %CI 0.1.06 to 1.26) and Clostridiales [o] (IVW: OR 1.15, 95 %CI 1.05 to 1.27) were associated with increased anxiety risk. Meta-analysis results indicated significant associations, particularly the protective effects of Actinobacteria (OR 0.90, 95 % CI, 0.83 to 0.98) and Clostridiaceae1 (OR 0.91, 95 % CI, 0.83 to 0.99) on depression and several taxa on anxiety. No significant instrumental variables for depression or anxiety on gut microbiota were identified.

Our findings highlight specific gut microbiota that are associated with depression and anxiety, underscoring the causal relationships between these intestinal microbes and psychiatric disorders. These results suggest potential strategies for mitigating disease symptoms and improving quality of life through microbiome-targeted therapies. Further studies, including randomized controlled trials and investigations into sex-specific effects, are essential to validate and expand upon these findings.

Depression is strongly linked to dysfunctions in the microbiota-gut-brain axis. Jasmine tea, a traditional Chinese beverage made by combining green tea with Jasminum sambac, has potential antidepressant effects. However, its potential to alleviate depression via modulation of the microbiota-gut-brain axis remains largely unstudied. In this study, we used a rat model of depression induced by chronic unpredictable mild stress (CUMS) to investigate the effects of jasmine tea extract (JT) on depression-related symptoms. Behavioral assessments, inflammatory marker analysis, hippocampal histology, and brain-derived neurotrophic factor (BDNF) expression assays demonstrated that JT alleviated depressive behaviors, reduced brain tissue damage, and restored cognitive function in CUMS-exposed rats. JT also significantly reduced intestinal levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and modulated oxidative stress markers (MDA, SOD, and CAT), suggesting a role in preserving intestinal integrity. Further, 16S rRNA sequencing revealed that JT shifted the gut microbiota composition in favor of beneficial bacteria such as Romboutsia, Blautia, and Monoglobus, while decreasing the abundance of potentially harmful bacteria, including Bifidobacterium, Clostridium_sensu_stricto_1, and Escherichia-Shigella. Meanwhile, non-targeted and targeted metabolomics analyses showed that JT influenced key metabolic pathways involving tryptophan, short-chain fatty acids, and bile acids, helping to restore metabolic balance across various tissues (feces, colon, serum, and cerebral cortex) in the depressed rats. These findings indicate that JT may alleviate depression by modulating the microbiota-gut-brain axis, highlighting its potential as a dietary intervention for depression management.

In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress.

During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol.

Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (p = .085 for Sweden, p = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (p = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor.

Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.

This study aimed to evaluate the impact of consumption of avocado oil (AO) and pulp (AP) on anxiety-like behavior, cerebral oxidative stress and alteration of the fecal microbiota in the mother and male Wistar rats offspring treated during gestation and lactation. Anxiety-like behavior was measured through the elevated plus maze (EPM) and open field test (OFT) tests. Cerebral malondialdehyde (MDA) and glutathione (GLUT) levels were measured in mothers and offspring. The fatty acid profile was determined for maternal milk and brain. Data showed a shorter time spent on the open arms of EPM in mothers and offspring for those fed AO and AP (P < 0.001). Moreover, the AO offspring adolescent and adult spent less time in the central area (P < 0.05). Furthermore, offspring adults from the AO moved about less and offspring from the AP ambulated more (P < 0.001). MDA was increased in mothers and decreased in the offspring in AO and AP and GLUT was lower in mothers and higher in adolescent and adult offspring in AP (P < 0.05). Polyunsaturated fatty acids in the brain and breast milk in AO and AP were decreased (P < 0.05). Furthermore, there was an increase in the abundance of intestinal bacteria related to the production of inflammatory metabolites that compromised brain function in offspring treated with avocado. These results suggest that avocado induces anxiogenic-like behavior and increases cerebral oxidative stress in mothers and offspring of rats treated during pregnancy and lactation, negatively altering the fecal microbiota of the offspring. So, we report for the first time how the consumption of avocado oil and pulp interferes with a developing organism when consumed in the early stages of life in rats.

Adolescent depression has profound impacts on physical, cognitive, and emotional development. While gut microbiota changes have been linked to depression, the relationship between oral microbiota and depression remains elusive. Our study aims to investigate the oral microbiota in treatment-naïve adolescents experiencing depression and examine their potential associations with cognitive function.

Our case-control study comprised two groups of adolescents aged 12-17: the depression group, including treatment-naïve individuals diagnosed with DSM-5 major depressive disorder (MDD), and a healthy control group of non-depressed individuals (HC). Participants underwent structured neuropsychiatric assessments, and fasting morning saliva samples were collected for the 16S rRNA sequencing to investigate the oral microbiota.

Significant differences were identified in the α- and β-diversities of the oral microbiota between MDD and HC groups. Specific bacterial taxa, including genera Streptococcus, Neisseria, Hemophilus, Fusobacterium, and g_norank_f_norank_o_Absconditabacteriales_SR1, were significantly associated with MDD. The association extends to cognitive functions, where correlations were observed between certain oral bacteria and cognitive scores, including instant and delayed memory, visual breadth, and speech features for the combined MDD and HC individuals (p < 0.05). Random forest analysis identified ten genera of oral microbes with the highest predictive values for MDD. The area under the curve (AUC) is 0.78 in the receiver operating characteristic (ROC) curve analysis.

Our results highlight the oral microbiota's role as a biomarker for adolescent depression and its impact on cognitive functions. These insights underscore the need for further research into the links between oral health, mental health, and cognitive functions.

Emerging evidence has highlighted that altered gut microbiota are associated with the onset and progression of depression via regulating the gut-brain axis. However, existing research has predominantly focused on children and adults, frequently neglecting adolescent depression. Given the rising prevalence and substantial impact of adolescent depression on functional impairment and suicidality, it is essential to focus more on this age group. In this study, we examined the fecal microbiota and inflammatory profiles of 99 depressed adolescents and 106 age-matched healthy controls using Illumina NovaSeq sequencing and multiplex immunoassays, respectively. Our findings revealed lower bacterial α-diversity and richness, alongside altered β-diversity in adolescents with depression. Gut dysbiosis associated with adolescent depression was characterized by increased pro-inflammatory genera such as Streptococcus and decreased anti-inflammatory genera like Faecalibacterium. These differential genera may serve as potential non-invasive biomarkers for adolescent depression, either individually or in combination. We also observed disruptions in the inferred microbiota functions in adolescent depression-associated microbiota, particularly in glycolysis and gluconeogenesis. Additionally, depressed adolescents exhibited systemic immune dysfunction, with elevated levels of pro-inflammatory cytokines and chemokines, which showed significant correlations with the differential genera. Our study bridges the gap between children and adults by providing new insights into the fecal microbiota characteristics and their links to immune system disruptions in depressed adolescents, which offer new targets for the diagnosis and treatment of depression in this age group.

Postpartum sleep disorder and mental disorders are common unpleasant conditions faced by women after delivery, and they have many adverse effects on both mothers and infants. It is unclear whether breast milk composition is affected by maternal sleep, psychological state, diet and gut microbiome. This study aims to explore the effects of these key factors on the functional protein components of breast milk.

With a prospective design, this pilot study included a total of 41 postpartum women. Breast milk and maternal faecal samples collected at 42 days and 3 months postpartum were tested by liquid chromatography-mass spectrometry and 16S RNA sequencing, respectively. Sleep state, psychological state and dietary intake data were also collected from the mothers with validated questionnaires.

In the early postpartum period, sleep disorders and depression were associated with a decrease in the functional proteins in breast milk. Disordered sleep was significantly negatively correlated with α-lactalbumin (cor = -0.578, p < 0.001), osteopontin (cor = -0.522, p < 0.01) and κ-casein (cor = -0.451, p < 0.01). Depression was negatively correlated with αs1-casein (cor = -0.422, p < 0.01), β-casein (cor = -0.317, p < 0.05) and casein (cor = -0.318, p < 0.05). In 3 months postpartum, most associations were disappeared. But a positive correlation was observed between β-casein (cor = 0.414, p < 0.01), casein (cor = 0.372, p < 0.05), total protein (cor = 0.376, p < 0.05) and depression, while a positive correlation was found between total protein (cor = 0.357, p < 0.05) and disordered sleep at 3 months postpartum. Faecal microbiome data illustrated that changes in the gut microbiome at early postpartum were associated with sleep disorders/depression, but not with the diet. Furthermore, functional pathway analysis revealed metabolic regulation in the amino acid synthesis and metabolic pathways associated with specific microbes was involved in the reduction of breast milk protein.

Sleep disorders/depression could lead to significant changes in breast milk profiles at 42 days postpartum. Maternal gut microbiome might affect breast milk protein composition through regulating amino acid synthesis and metabolic pathways.

Recent studies suggest a link between gut microbiota and neurological diseases, implicating the microbiome's role in neurological health. However, the specific alterations in the microbiome associated with migraine remain underexplored. This study aims to systematically review the existing literature to determine whether migraine patients are associated with changes in gut microbiota composition.

A systematic review was conducted in accordance with the PRISMA statement. We included original empirical studies investigating the microbiome in migraine patients. Data extracted included study design, participant demographics, microbiome differences at various taxonomic levels, and measures of microbial diversity (alpha and beta diversity). The search and selection process involved four independent reviewers who assessed abstracts and full texts to ensure eligibility. The gut microbiota was evaluated using relative abundance and diversity indices.

Six studies, encompassing various regions including China, Korea, and Italy, were included in the analysis. The results indicated significant differences in gut microbiota between migraine patients and controls. Key findings include a reduction in Faecalibacterium, a genus known for its anti-inflammatory properties, in migraine patients, including those with chronic migraine. Conversely, Veillonella exhibited elevated abundance compared to controls. Other taxa, such as Prevotella and Parabacteroides, showed variable associations with migraine across different studies, suggesting a dysbiotic gut environment in migraine patients.

This review highlights that migraines are associated with specific alterations in gut microbiota, including decreased microbial diversity and changes in the abundance of key taxa. These findings suggest that gut microbiota dysbiosis may play a role in migraine pathophysiology. Further research is needed to explore the potential causal relationships and therapeutic implications, particularly targeting the microbiome in migraine management.

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.

Neuropsychiatric diseases encompass a range of mental and neurological disorders that have a significant and far-reaching effect on an individual's quality of life. These conditions affect not only the mental status but also the physical well-being of individuals, which leads to weakened immune systems and other diseases. Emerging research underscores a significant connection between the gut microbiome and neuropsychiatric diseases, suggesting that microbial communities within the gastrointestinal tract may influence brain function and mental health. Gut dysbiosis is caused by various factors, including stress, diet, inappropriate usage of antibiotics, infections, and so on, all of which can disrupt numerous pathways, resulting in abnormal neurotransmitter signaling, inflammation, and impaired brain function. Similarly, various neuropsychiatric diseases can disrupt the specific microbiome in the gut, leading to gut dysbiosis, often impairing memory and cognitive function. The growing evidence supporting the role of gut dysbiosis in neuropsychiatric disorders has opened up new avenues for therapeutic interventions. Modulating the gut microbiome through strategies such as probiotics, prebiotics, or fecal microbiota transplantation has shown promising results in various studies of neuropsychiatric disorders. However, further research is needed to fully elucidate the mechanisms involved in gut dysbiosis-associated brain changes to develop effective and personalized treatment strategies for neuropsychiatric diseases.

Human sleep quality is intricately linked to gut health. Emerging research indicates that Bifidobacterium animalis subsp. lactis BLa80 has the potential to ameliorate gut microbiota dysbiosis. This randomized, placebo-controlled study evaluated the impact of BLa80 supplementation on sleep quality and gut microbiota in healthy individuals. One hundred and six participants were randomly assigned to receive either a placebo (maltodextrin) or BLa80 (maltodextrin + BLa80 at 10 billion CFU/day) for 8 weeks. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI), a validated tool consisting of 18 items assessing seven components of sleep quality over a one-month period, and the Insomnia Severity Index (ISI), a secondary measure of insomnia severity. Gut microbiota changes were assessed using 16S rRNA sequencing, while the in vitro gamma-aminobutyric acid (GABA) production capacity of BLa80 was analyzed by HPLC. After 8 weeks, the intervention group exhibited a significant reduction in the PSQI total score compared to the placebo group, suggesting improved sleep quality. While no significant changes in alpha diversity were noted, beta diversity differed markedly between groups. The gut microbiota predominantly consisted of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Fusobacteria, collectively accounting for over 99.9% of the gut microbiota. Statistical analysis showed that BLa80 significantly decreased the relative abundance of Proteobacteria phylum and increased the abundance of Bacteroidetes, Fusicatenbacter, and Parabacteroides compared to placebo. PICRUSt2 analysis indicated noteworthy enhancements in the pathways of purine metabolism, glycolysis/gluconeogenesis, and arginine biosynthesis due to BLa80 intervention. Moreover, BLa80 demonstrated notable GABA production, potentially contributing to its effects on sleep quality modulation. These results demonstrate the ability of BLa80 to improve sleep quality through modulating gut microbiota and GABA synthesis, highlighting its potential as a beneficial probiotic strain.

The microbiota-gut-brain-axis (MGBA) plays a role in the aetiology of mental disorders. Depression, a leading cause of disability worldwide, may be improved by probiotics. The aim of this narrative review is to investigate and synthesize the current evidence linking probiotic food supplementation with depressive symptomology.

The gut and the brain communicate and interact via the MGBA through inflammation and the immune system, short chain fatty acid production, neuronal innervation and activation as well as endocrine and neurotransmitter modulation. Dysregulation of gut-brain pathways are caused by gut dysbiosis and implicated in the onset, persistence and exacerbation of depression related symptoms. Modulation of the gut microbiota via administration of probiotics has shown to reduce depressive symptom severity with Bifidobacterium and Lactobacillus strains being the most reported. Probiotics may produce greater benefits in mild depression rather than in chronic, treatment resistant depression. Probiotic supplementation is a promising and safe approach for the prevention of severe depressive disorders in high-risk individuals such as people with subthreshold depression. However, the mechanistic pathways of the MGBA require further investigation and additional human clinical trials are necessary to evaluate the role of probiotics on depression.

Anxiety and depression are common non-motor symptoms of Parkinson's disease (PD) that significantly affect patients' quality of life. In recent years, our understanding of PD has advanced through multifaceted studies on the pathological mechanisms associated with anxiety and depression in PD. These classic psychiatric symptoms involve complex pathophysiology, with both distinct features and connections to the mechanisms underlying the aetiology of PD. Furthermore, the co-occurrence of anxiety and depression in PD blurs the boundaries between them. Therefore, a comprehensive summary of the pathogenic mechanisms associated with anxiety and depression will aid in better addressing the emergence of these classic psychiatric symptoms in PD. This article integrates neuroanatomical, neural projection, neurotransmitter, neuroinflammatory, brain-gut axis, neurotrophic, hypothalamic-pituitary-adrenal axis, and genetic perspectives to provide a comprehensive description of the core pathological alterations underlying anxiety and depression in PD, aiming to provide an up-to-date perspective and broader therapeutic prospects for PD patients suffering from anxiety or depression.

Major depressive disorder (MDD) is a severe affective disorder that is clearly linked to stroke and diabetes. This study aimed to investigate the mediating role of stroke and diabetes in the association between the cardiometabolic index (CMI) and MDD.

This cross-sectional study analyzed data from 8312 participants in the National Health and Nutrition Examination Survey (NHANES, 2005-2018). MDD was diagnosed using the Patient Health Questionnaire-9 (PHQ-9; score > 10). Associations were evaluated using multivariate logistic/linear regression, stratified interaction analyses, restricted cubic spline (RCS) models for nonlinearity, and bootstrap mediation testing.

There was a robust positive correlation between the incidence of MDD [OR = 1.36 (95 % CI: 1.21-1.51)] and the PHQ-9 score [β = 0.55 (95 % CI: 0.37-0.73)], with a one-unit increase in CMI. The participants in CMIQ4 had a 64 % greater risk of stroke than did the participants in CMIQ1 [OR = 1.64 (95 % CI: 1.17-2.29)]. The forest plot shows that the results remained stable under the grouping of stroke, diabetes, race, gender, and age. Moreover, stroke and diabetes both exhibited partial mediating roles, with indirect effects accounting for 4.03 % and 5.37 % of the total effect, respectively. Through RCS analysis, a nonlinear correlation was observed between CMI and MDD and between CMI and diabetes. There is a linear relationship between stroke and MDD, and maintaining CMI levels below 0.518 may mitigate the risk of MDD.

Stroke and diabetes partially mediated the associations between CMI and MDD. However, additional prospective studies are warranted to scrutinize the impact of CMI on MDD.

Sleep is essential for physical and mental health. However, stress-related sleep disorders are common in Japan, and the gut-brain axis may play a role in sleep and stress management. This study investigated whether the consumption of granola containing multiple prebiotic ingredients could alleviate stress and improve insomnia in adults with stress-related sleep problems, regardless of individual differences in the gut microbiota. Additionally, we aimed to investigate the relationship between changes in gut microbiota and the observed improvements.

A single-arm uncontrolled trial was conducted with 27 adults with high stress levels and sleep disturbance. The participants consumed 50 g of prebiotics-containing granola daily for 8 weeks. Subjective sleep quality was assessed using the Athens Insomnia Scale, Epworth Sleep Scale, and Oguri-Shirakawa-Azumi Sleep Inventory-Middle-aged and Aged version (OSA-MA). Stress levels were assessed by administering the Brief Job Stress Questionnaire and Profile of Mood States 2nd edition (POMS2). Gut microbiota composition was analyzed using 16S rDNA sequencing.

After 8 weeks, subjective insomnia scores and sleep onset and maintenance improved significantly, whereas the stress and mood disturbance scores decreased significantly. Gut microbiota analysis showed that the relative abundance of Bifidobacterium increased, whereas that of Bacteroides decreased. Correlation analysis suggested a significant association between increased Bifidobacterium level and reduced stress (r = -0.39, p = 0.0035) and insomnia levels (r = -0.3, p = 0.026).

Prebiotics-containing granola improved subjective sleep quality and reduced stress in adults with stress-related sleep disturbances, which may be attributed to alterations in gut microbiota, particularly the increase in Bifidobacterium abundance.

Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression.

To investigate the relationship between Hcy, microbiome, and cognition in depressive patients.

We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function.

Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).

Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.

Depression exhibits a complex and multifaceted pathophysiology, accompanied by high rates of relapse and disability with current medication treatments. 5-Hydroxytryptophan (5-HTP) is a promising candidate for depression therapy, but its poor pharmacokinetics hinders its clinical application. To address this limitation, we introduced the hydroxylase XcP4H into Escherichia coli Nissle 1917 (EcN) to biosynthesize 5-HTP in vivo. To create a high-yielding EcN strain for 5-HTP production, we engineered XcP4H through enzyme-directed evolution using a novel genetic code expansion-based high-throughput screening method. The most effective XcP4H variant achieved a 22-fold increase in 5-HTP production, and molecular dynamic simulations elucidated the underlying mechanisms. After pathway engineering and gene editing, we further improved the 5-HTP yield in EcN. When the most robust strain, EcN@5-HTP, was employed as a live therapeutic, it alleviated depressive-like behaviors in mice by increasing 5-HT levels in both the gut and brain, repairing neurological abnormalities, inhibiting inflammation, elevating SCFAs concentrations, and modulating gut microbiota dysbiosis. By integrating synthetic biology with enzyme-directed evolution, we successfully addressed the pharmacokinetic limitations of 5-HTP through a live therapeutic approach. This proof-of-concept design clearly demonstrates that combining synthetic biology with probiotics has the potential to significantly revolutionize our strategies for disease detection, prevention, and treatment.

There is mounting evidence for the involvement of the immune system, neuroinflammation and disturbed gut microbiota, or dysbiosis, in attention-deficit/hyperactivity disorder (ADHD). Gut dysbiosis is strongly implicated in many physical, autoimmune, neurological, and neuropsychiatric conditions, however knowledge of its particular pathogenic role in ADHD is sparse. As such, this narrative review examines and synthesizes the available evidence related to inflammation, dysbiosis, and neural processes in ADHD. Minimal differences in microbiota diversity measures between cases and controls were found, however many relative abundance differences were observed at all classification levels (phylum to strain). Compositional differences of taxa important to key gut-brain axis pathways, in particular Bacteroides species and Faecalibacterium, may contribute to inflammation, brain functioning differences, and symptoms, in ADHD. We have identified one possible model of ADHD etiopathogenesis involving systemic inflammation, an impaired blood-brain barrier, and neural disturbances as downstream consequences of gut dysbiosis. Nevertheless, studies conducted to date have varied degrees of methodological rigour and involve diverse participant characteristics and analytical techniques, highlighting a need for additional research.

Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS.

Global metabolomics was performed in an observational cohort of people with MS, followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2 g/day) or placebo for 16 weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory, and gut microbiome parameters.

In the observational cohort, higher primary bile acid levels at baseline predicted slower whole-brain atrophy, brain substructure atrophy, and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not differ significantly between arms (p = 0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4+ and Th1/17 cells decreased, while CD4+ naive cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted between the two groups.

Bile acid metabolism in MS is linked to brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration.

National MS Society grant RG-1707-28601 to P.B., R01 NS082347 from the National Institute of Neurological Disorders and Stroke to P.A.C., and National MS Society grant RG-1606-08768 to S.S.

Depression is a mental disorder, and genistein is known to have antidepressant effects, but its mechanism of action is still unclear. Here, the mechanism of genistein improving depression based on gut microbiota was explored using classic behavioral indicators of depression combined with genomic technology. The behavioral evaluation showed that rats gavaged with 20-40 mg/kg genistein showed an increase in body weight, glucose preference, absenteeism score, body temperature, and 5-hydroxytryptamine (5-HT) content, while a decrease in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) content compared to the depression rat model group, but there was no significant difference compared to the positive control (fluoxetine). The results of high-throughput sequencing showed that genistein increased the relative abundance of Firmicutes and Actinobacteriota and decreased the relative abundance of Bacteroidota at the phylum level. At the genus level, the abundance of Bifidobacterium, a short-chain fatty acid producing bacterium, was increased. Furthermore, metagenome results revealed that the antidepressant effect of genistein can be achieved by promoting glutamate metabolism, increasing glutamic acid decarboxylase (GAD) expression levels, promoting γ-aminobutyric acid (GABA) synthesis, and indirectly increasing 5-HT levels.

The paper explores the intricate bidirectional relationship between depression and obesity, emphasizing that each condition increases the risk of the other. Shared biologic mechanisms, such as neuroinflammation, dysregulation of the hypothalamic-pituitary-adrenal axis, and dysfunction of the gut-brain axis, contribute to the co-occurrence of these conditions. In addition, the emerging social withdrawal syndrome, hikikomori, is suggested as an associated socio-behavioral factor with the comorbidity of depression and obesity. Among antidepressants, selective serotonin reuptake inhibitors and bupropion (a norepinephrine/dopamine reuptake inhibitor), but not tricyclic antidepressants, are considered pharmacotherapeutic options for the co-occurrence of depression and obesity.

Perinatal depression and anxiety pose significant risks to maternal health and may lead to suicide. The gut microbiota may play a crucial role in perinatal depression and anxiety. However, the relationship between the alterations in gut microbiota and perinatal depression and anxiety remains unclear. This study aimed to investigate the dynamic changes of gut microbiota over various perinatal stages and their associations with perinatal depression and anxiety symptoms, especially suicide ideation.

A total of 177 pregnant and 19 postpartum women were recruited in this study, with 48 of them participating longitudinally. Maternal depression and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), 9-item Patient Health Questionnaire (PHQ-9), and 7-item Generalized Anxiety Disorder Scale (GAD-7). Fecal samples collected during the perinatal period were analyzed using 16S rRNA gene sequencing.

Significant changes in microbial diversity and multi-taxonomic levels were observed during pregnancy. The random forest regression model showed significant associations of some gut microbial features with depression and anxiety symptoms. Several genera were significantly associated with gestation age and perinatal depression and anxiety, such as Akkermansia, Bifidobacterium and Streptococcus. In addition, Erysipelotrichaceae_UCG-003 and Eubacterium_hallii_group were positively associated with suicidal ideation. The glycine biosynthesis pathway might act as a mediator between Eubacterium_hallii_group and suicidal ideation (ab = 3.27, p < 0.05).

The gut microbiota undergoes a programmed shift during pregnancy, which may play a critical role in perinatal depression and anxiety. Our findings underscore the impact of certain bacterial genera and metabolic pathways on perinatal mental health, which may help to develop new diagnostic tools and targeted interventions to reduce perinatal mental disorders and improve the outcomes for both mothers and infants.

Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.

Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.

The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.

Modern habits are becoming more and more disruptive to health. As our days are often filled with circadian disruption and stress exposures, we need to understand how our responses to these external stimuli are shaped and how their mediators can be targeted to promote health. A growing body of research demonstrates the role of the gut microbiota in influencing brain function and behavior. The stress response and circadian rhythms, which are essential to maintaining appropriate responses to the environment, are known to be impacted by the gut microbiota. Gut microbes have been shown to alter the host's response to stress and modulate circadian rhythmicity. Although studies demonstrated strong links between the gut microbiota, circadian rhythms and the stress response, such studies were conducted in an independent manner not conducive to understanding the interface between these factors. Due to the interconnected nature of the stress response and circadian rhythms, in this review we explore how the gut microbiota may play a role in regulating the integration of stress and circadian signals in mammals and the consequences for brain health and disease.

The geriatric population, comprising ages 65 and above, encounters distinct health obstacles because of physiological changes and heightened vulnerability to diseases. New technologies are being investigated to tackle the intricate health requirements of this population. Recent advancements in probiotics and nanotechnology offer promising strategies to enhance geriatric health by improving nutrient absorption, modulating gut microbiota, and delivering targeted therapeutic agents. Probiotics play a crucial role in maintaining gut homeostasis, reducing inflammation, and supporting metabolic functions. However, challenges such as limited viability and efficacy in harsh gastrointestinal conditions hinder their therapeutic potential. Advanced nanotechnology can overcome these constraints by enhancing the efficacy of probiotics through nano-encapsulation, controlled delivery, and improvement of bioavailability. This review explores the synergistic potential of probiotics and advanced nanotechnology in addressing age-related health concerns. It highlights key developments in probiotic formulations, nano-based delivery systems, and their combined impact on gut health, immunity, and neuroprotection. The convergence of probiotics and nanotechnology represents a novel and transformative approach to promoting healthy aging, paving the way for innovative therapeutic interventions.

Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 51 participants (Mage = 49.56, SD = 13.31) receiving an immersive psychosocial intervention. A total of 142 multi-omics samples were collected from participants before, during, and three months after the nine-day inquiry-based stress reduction program.

Results revealed that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1.

These findings reveal a potentially protective link between the Prevotella-dominant microbiome and depression, as evidenced by a reduced pro-inflammatory environment and fewer depressive symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, may highlight potential avenues for microbiome-targeted therapies for managing depression.

Kratom (Mitragyna speciosa), a plant native to Southeast Asia, is commonly used as a supplement for fatigue, pain relief, mood enhancement, and euphoria. Kratom extract exhibits diverse pharmacological properties, including antioxidant, anti-inflammatory, and gastrointestinal effects, with studies showing its ability to modulate gut microbiota and stimulate beneficial bacteria growth. Given these properties, kratom treatment may produce significant effects in a rat model, warranting further investigation.

Male Wistar rats were administered kratom extract orally on a daily basis for 28 days. Fresh fecal samples were collected and analyzed for changes in gut microbiome composition using 16S rRNA sequencing. Hematological parameters and lipid profiles were also measured to evaluate any systemic effects.

The administration of kratom extract did not significantly affect hematological parameters or lipid profiles. However, notable changes were observed in gut microbiota composition, with significant increases in specific bacteria such as Candidatus Stoquefichus and Prevotellaceae UCG-001, and a decrease in Corynebacterium. LEfSe and cladogram analyses corroborated the higher prevalence of Candidatus Stoquefichus, Prevotellaceae UCG-001, and Erysipelatoclostridiaceae in the kratom treatment group compared to controls.

Kratom extract significantly alters gut microbiome composition in rats, promoting beneficial bacteria while also elevating certain taxa associated with negative health outcomes. These mixed effects highlight the need for further research on the long-term implications of kratom use for gut health and its broader health consequences, as well as potential therapeutic applications.

Not applicable.

This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.

In addition to the known link between cholecystectomy and depression, the risk of developing short-term and long-term depression after surgery and whether such mental health issues leads to suicide were not known. Therefore, this study aimed to address these questions. Using data from the National Health Insurance Service of Korea (2002-2019), we conducted a retrospective cohort study including 6,688 cholecystectomy patients matched with 66,880 individuals without a history of cholecystectomy for suicide analysis and 6,694 cholecystectomy patients matched with 66,940 individuals for depression analysis. The non-cholecystectomy group was matched at a 1:10 ratio for sex and age. The incidence of depression and suicide were followed from the day of cholecystectomy to December 31, 2019. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression. Short-term depression risk within three years of cholecystectomy was significantly elevated (aHR 1.38, 95% CI 1.19-1.59), while the long-term depression risk beyond three years was not significantly greater (aHR 1.09, 95% CI 0.98-1.22). Cholecystectomy was not associated with an increased risk of suicide in any period. These findings highlight the importance of monitoring and providing postoperative mental health support for patients at risk of short-term depression after cholecystectomy. However, no association was observed with long-term depression or suicide risk.

The microbiota-gut-brain axis plays a pivotal role in neuropsychiatric disorders, particularly in depression. Escitalopram (ESC) is a first-line antidepressant, however, its regulatory mechanisms on the microbiota-gut-brain axis in the treatment of depression remain unclear. The antidepressant effects of ESC were evaluated using the forced swim test in Wistar-Kyoto (WKY) rats, while damage in the gut and brain regions was assessed through H&E staining and immunohistochemistry. The therapeutic mechanisms in WKY rats with depression-like behavior were investigated through 16S rRNA sequencing of the gut microbiota, serum untargeted metabolomics, and hippocampal proteomics. Results indicated that ESC intervention improved depressive-like behaviors, as evidenced by increased swimming times in WKY rats, and also restored intestinal permeability and brain tissue integrity. Significant changes in the gut microbiota composition, particularly an increase in Bacteroides barnesiae, as well as increases in serum sphingolipid metabolites (Sphinganine 1-phosphate, Sphingosine, and Sphingosine-1-phosphate) and hippocampal proteins (Sptlc1, Enpp5, Enpp2), were strongly correlated. These robust correlations suggest that ESC may exert its antidepressant effects by modulating sphingolipid metabolism through the influence of gut microbiota. Accordingly, this research elucidates novel mechanisms underlying the antidepressant efficacy of ESC and highlights the pivotal importance of the microbiota-gut-brain axis in mediating these effects.

Persistent post-surgical pain (PPSP) occurs in a proportion of patients following surgical interventions. Research suggests that specific microbiome components are important for brain development and function, with recent studies demonstrating that chronic pain results in changes to the microbiome. Consumption of a high fat, high sugar (HFHS) diet can drastically alter composition of the microbiome and is a modifiable risk factor for many neuroinflammatory conditions. Therefore, we investigated how daily consumption of a HFHS diet modified the development of PPSP, brain structure and function, and the microbiome. In addition, we identified significant correlations between the microbiome and brain in animals with PPSP. Male and female rats were maintained on a control or HFHS diet. Animals were further allocated to a sham or surgery on postnatal day (p) p35. The von Frey task measured mechanical nociceptive sensitivity at a chronic timepoint (p65-67). Between p68-72 rats underwent in-vivo MRI to examine brain volume and diffusivity. At p73 fecal samples were used for downstream 16 s rRNA sequencing. Spearman correlation analyses were performed between individual microbial abundance and MRI diffusivity to determine if specific bacterial species were associated with PPSP-induced brain changes. We found that consumption of a HFHS diet exacerbated PPSP in adolescents. The HFHS diet reduced overall brain volume and increased white and grey matter density. The HFHS diet interacted with the surgical intervention to modify diffusivity in numerous brain regions which were associated with specific changes to the microbiome. These findings demonstrate that premorbid characteristics can influence the development of PPSP and advance our understanding of the contribution that the microbiome has on function of the brain-microbiota-gut axis.

Parental substance abuse increases the risk of neurological and psychiatric disorders in offsprings. However, its underlying mechanism remains elusive. Our previous study demonstrated that long-term exposure to methamphetamine (Meth), a psychostimulant drug with high addiction potential, remarkably alters the gut microbiome and metabolites in male mice, which contribute to Meth-induced anxiety-like behaviors. The current study aimed to investigate whether gut microbiota and metabolism serve as potential peripheral targets for transgenerational mental problems by paternal Meth exposure. We found that paternal Meth exposure induced depression-like behaviors both in the first (F1) and the second (F2) generations of male mice. Further, the depletion of gut bacteria through antibiotic treatments normalized the depression-like behaviors to normal levels in both F1 and F2 male mice. Then, alterations in gut bacterial composition were observed in both F1 and F2 male mice. Specifically, Eubacterium_ruminantium_group, Enterorhabdus, Alloprevotella, and Parabacteroides were the commonly affected bacterial taxa in F1 and F2 male mice. In addition, the results of alterations in gut metabolism showed that LPC 14:1-SN1 emerged as the consistently altered metabolite in the colons of F1 and F2 male mice. Taken together, our findings provide the first evidence that paternal Meth exposure enhances depression-like behaviors in F1 and F2 male mice, potentially mediated by the gut microbiome and metabolism.

Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed.

Quinoa, rich in pharmacologically active ingredients, possesses the potential benefit in preventing cognitive impairments induced by hypoxia. In this study, the efficacy of quinoa ethanol extracts (QEE) consumption (200 and 500 mg/kg/d, respectively) against hypobaric hypoxia (HH)-induced cognitive deficits in mice was investigated. QEE significantly ameliorated hypoxic stress induced by HH, as evidenced by improvements in baseline indices and reductions in hypoxia-inducible factor 1α levels. Furthermore, QEE enhanced antioxidant defense mechanisms, alleviated neuroinflammation in brain regions associated with memory, and improved HH-induced cognitive impairments by modulating the cyclic adenosine monophosphate response element-binding protein/brain-derived neurotrophic factor signaling pathway. Higher doses generally yielded more effective outcomes than lower doses. QEE also significantly reshaped the gut microbiome structure of HH mice, inhibited gut barrier damage, and reduced lipopolysaccharide migration, thereby increasing short-chain fatty acids (SCFAs) levels. Our findings suggest that QEE may be a promising strategy for preventing hypoxia-induced cognitive impairments by maintaining gut microbiome stability and increasing SCFAs levels.

This review explores the intricate relationships among the gut microbiota, dietary patterns, and mental health, focusing specifically on depression. It synthesizes insights from microbiological, nutritional, and neuroscientific perspectives to understand how the gut-brain axis influences mood and cognitive function.

Recent studies underscore the central role of gut microbiota in modulating neurological and psychological health via the gut-brain axis. Key findings highlight the importance of dietary components, including probiotics, prebiotics, and psychobiotics, in restoring microbial balance and enhancing mood regulation. Different dietary patterns exhibit a profound impact on gut microbiota composition, suggesting their potential as complementary strategies for mental health support. Furthermore, mechanisms like tryptophan metabolism, the HPA axis, and microbial metabolites such as SCFAs are implicated in linking diet and microbiota to depression. Clinical trials show promising effects of probiotics in alleviating depressive symptoms. This review illuminates the potential of diet-based interventions targeting the gut microbiota to mitigate depression and improve mental health. While the interplay between microbial diversity, diet, and brain function offers promising therapeutic avenues, further clinical research is needed to validate these findings and establish robust, individualized treatment strategies.