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Integrated multi-omics analysis of gut microbiome and serum metabolome in unipolar and bipolar depression.
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Gut Microbiome Composition Linked to Inflammatory Factors and Cognitive Functions in First-Episode, Drug-Naive Major Depressive Disorder Patients.
OBJECTIVE: The microbiota-gut-brain axis, especially the inflammatory pathway, may play a critical role in the pathogenesis of cognitive impairment in major depressive disorder (MDD). However, studies on the microbiota-inflammatory-cognitive function axis in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and explore the correlation between gut microbiota and inflammatory factors, cognitive function in MDD patients. METHOD: Study participants included 66 first-episode, drug naïve MDD patients as well as 43 healthy subjects (HCs). The composition of fecal microbiota was evaluated using16S rRNA sequencing and bioinformatics analysis. The cytokines such as hs-CRP, IL-1β, IL-6, IL-10, and TNF-α in peripheral blood were detected via enzyme linked immunosorbent assay (ELISA); assessment of cognitive functions was performed using the Color Trail Test (CTT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (SCWT). RESULTS: We found that compared with HCs, MDD patients had cognitive impairments and showed different α-diversity and β-diversity of gut microbiota composition. LDA effect size (LEfSe) analysis found MDD have higher Deinococcaceae and lower Bacteroidaceae, Turicibacteraceae, Clostridiaceae and Barnesiellaceae at family level. Deinococcus and Odoribacter was higher in the MDD group, however, Bacteroides, Alistipes, Turicibacter, Clostridium, Roseburia, and Enterobacter were lower at genus level. Furthermore, In MDD patients, the Bacteroidaceae and Bacteroides were both positively correlated with hsCRP, CCT1, CCT2. Alistipes was positively correlated with IL-6, Word time, Color time, Word-Color time, Color-Word time and negatively correlated with Delayed Memory, Total score and Standardized score. Turicibacteraceae and Turicibacter were both negatively correlated with IL-1β and IL-6. CONCLUSION: The present findings confirm that the gut microbiota in MDD patients have altered gut microbes that are closely associated with inflammatory factors and cognitive function in MDD patients.
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Nutritional Psychiatry: Where to Next?
The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and 'psychobiotic' interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.
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Isoalantolactone relieves depression-like behaviors in mice after chronic social defeat stress via the gut-brain axis.
RATIONALE: The management of depression continues to be challenging despite the variety of available antidepressants. Herbal medicines are used in many cultures but lack stringent testing to understand their efficacy and mechanism of action. Isoalantolactone (LAT) from Elecampane (Inula helenium) improved the chronic social defeat stress (CSDS)-induced anhedonia-like phenotype in mice comparable to fluoxetine, a selective serotonin reuptake inhibitor (SSRI). OBJECTIVES: Compare the effects of LAT and fluoxetine on depression-like behaviors in mice exposed to CSDS. RESULT: The CSDS-induced decrease in protein expression of postsynaptic density (PSD95), brain derived neurotrophic factor (BDNF), and glutamate receptor subunit-1 (GluA1) in the prefrontal cortex was restored by LAT. LAT showed robust anti-inflammatory activity and can lessen the increase in IL-6 and TNF-α caused by CSDS. CSDS altered the gut microbiota at the taxonomic level, resulting in significant changes in α- and β-diversity. LAT treatment reestablished the bacterial abundance and diversity and increased the production of butyric acid in the gut that was inhibited by CSDS. The levels of butyric acid were negatively correlated with the abundance of Bacteroidetes, and positively correlated with those of Proteobacteria and Firmicutes across all treatment groups. CONCLUSIONS: The current data suggest that, similar to fluoxetine, LAT show antidepressant-like effects in mice exposed to CSDS through the modulation of the gut-brain axis.
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Potential role of gut microbiota in major depressive disorder: A review.
Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.
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Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role.
Stroke-induced depression is a common complication and an important risk factor for disability. Besides psychiatric symptoms, depressed patients may also exhibit a variety of gastrointestinal symptoms, and even take gastrointestinal symptoms as the primary reason for medical treatment. It is well documented that stress may disrupt the balance of the gut microbiome in patients suffering from post-stroke depression (PSD), and that disruption of the gut microbiome is closely related to the severity of the condition in depressed patients. Therefore, maintaining the balance of intestinal microbiota can be the focus of research on the mechanism of acupuncture in the treatment of PSD. Furthermore, stroke can be effectively treated with acupuncture at all stages and it may act as a special microecological regulator by regulating intestinal microbiota as well. In this article, we reviewed the studies on changing intestinal microbiota after acupuncture treatment and examined the existing problems and development prospects of acupuncture, microbiome, and poststroke depression, in order to provide new ideas for future acupuncture research.
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Correction: Systematic review of bidirectional interaction between gut microbiome, miRNAs, and human pathologies.
[This corrects the article DOI: 10.3389/fmicb.2025.1540943.].
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Lactobacillus paracasei PS23 reduced early-life stress abnormalities in maternal separation mouse model.
Maternal separation (MS) has been developed as a model for inducing stress and depression in studies using rodents. The concept of the gut-brain axis suggests that gut health is essential for brain health. Here, we present the effects of administration of a probiotic, Lactobacillus paracasei PS23 (PS23), to MS mice against psychological traits including anxiety and depression. The administration of live and heat-killed PS23 cells showed positive behavioural effects on MS animals, where exploratory tendencies and mobility were increased in behavioural tests, indicating reduced anxiety and depression compared to the negative control mice (P<0.05). Mice administered with both live and heat-killed PS23 cells also showed lower serum corticosterone levels accompanied by higher serum anti-inflammatory interleukin 10 (IL-10) levels, compared to MS separated mice (P<0.05), indicating a stress-elicited response affiliated with increased immunomodulatory properties. Assessment of neurotransmitters in the brain hippocampal region revealed that PS23 affected the concentrations of dopaminergic metabolites differently than the control, suggesting that PS23 may have improved MS-induced stress levels via neurotransmitter pathways, such as dopamine or other mechanisms not addressed in the current study. Our study illustrates the potential of a probiotic in reversing abnormalities induced by early life stress and could be an alternative for brain health along the gut-brain axis.
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Gut Microbiota in Depression: A Focus on Ketamine.
According to the WHO, major depressive disorder is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. The pathophysiology of this common and chronic disease is still not completely understood. The gut microbiome is an increasingly recognized environmental factor that can have a role in depression, acting through the gut-microbiota-brain axis. The available treatment for depression is still insufficient since 30% of patients are treatment-resistant. There is an unquestionable need for novel strategies. Ketamine is an effective antidepressant in treatment-resistant patients. It is suggested that the antidepressant effect of ketamine may be partially mediated by the modification of gut microbiota. In this study, we presented a review of data on gut microbiota in depression with special attention to the effect of ketamine on the microbiome in animal models of depression. Earlier reports are preliminary and are still insufficient to draw firm conclusion, but further studies in this field might help to understand the role of the gut-brain axis in the treatment of depression and might be the ground for developing new effective treatment strategies.
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Investigating acupuncture therapy in depression: mechanisms of synaptic plasticity regulation.
Depression is a severe heterogeneous mental illness that is highly co-morbid with other mental and somatic disorders. It poses a significant healthcare burden on both individuals and society. Currently, the use of single-target antidepressants exhibits suboptimal efficacy with significant adverse effects. Acupuncture has been advocated as a practical and effective treatment for depression, due to its low adverse effects rate compared to antidepressant medication. Currently, several studies have shown that acupuncture treatment for depression primarily involves multiple therapeutic mechanisms, including the regulation of specific gene expression, neuropeptide and neurotransmitter release, increasing the expression of neurotrophic factors, suppressing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, attenuating inflammatory responses, and restoring gut microbiota balance. These therapeutic effects involve the regulation of critical signaling pathways, including the cAMP-responsive element binding protein (CREB) signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, mechanistic target of rapamycin (mTOR) signaling pathway, and toll-like receptors (TLR) signaling pathway. Notably, depression-associated molecular mechanisms and signaling pathway dysregulations are closely linked to impaired neural and synaptic plasticity. Acupuncture synergistically modulates the neuro-immune-microbiome multidimensional network and integrates crosstalk among key pathways such as CREB, thereby systemically restoring synaptic plasticity. This multi-dimensional integrative mechanism likely underlies its therapeutic superiority over single-target antidepressants. This review aims to elucidate how acupuncture restores cerebral synaptic plasticity by rectifying depression-related systemic dysfunctions and signaling pathway abnormalities, which will advance our understanding of its regulatory potential in depression treatment and inform the development of precision therapeutic strategies.