Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 3 204
Page 132 of 321-
Next-generation microbiome therapeutics: psychobiotics and fecal microbiota transplants for mental health treatment.
The human gastrointestinal tract (GIT) harbors a diverse microbial community, collectively referred to as gut microbiota, which plays an essential role in maintaining host physiology, metabolism, immune function, and neurobehavioral processes. Mounting evidence highlights the importance of the bidirectional Gut-brain (GB) axis, through which gut microbes influence neural signalling, stress response, and emotional regulation. Dysbiosis of this axis has been associated with psychiatric, neurodevelopmental, and neurodegenerative disorders, such as anxiety, autism spectrum disorder (ASD), major depressive disorder (MDD) and schizophrenia. A growing area of research has identified psychobiotics-live microorganisms with psychotropic potential-as promising therapeutic agents for mental health conditions. These microbes exert their effects through multiple mechanisms, including modulation of neurotransmitter production, short-chain fatty acid (SCFA) signalling, immune regulation, and hypothalamic-pituitary-adrenal (HPA) axis stabilization. Preclinical and clinical studies provide supportive evidence for their antidepressant and anxiolytic effects, although large-scale, long-term trials remain limited. In parallel, fecal microbiota transplantation (FMT) has emerged as a potential strategy to restore microbial balance and improve psychiatric symptoms. Early findings demonstrate its role in modulating immune pathways, such as NLRP3 inflammasome signalling, and neurotrophic factors via gut microbial reshaping. Together, psychobiotics and FMT represent next-generation microbiome therapeutics that may complement conventional psychiatric interventions. This review synthesizes current evidence and highlights the future potential of microbiome-based strategies in treating mental health disorders.
-
Bidirectional interactions between St. John´s wort and gut microbiome: Potential implications on gut-brain-axis.
Emerging evidence highlights the role of gut microbiome in mental health disorders, including depression, raising the question whether the action of antidepressants could be mediated, at least in part, via the microbiome-gut-brain axis. To explore this, we subjected a St. John's wort extract (STW 3-VI), clinically proven to be effective in mild to moderate depression, to a model of the upper and lower intestinal tract, including static in vitro predigestion followed by ex vivo incubation with human microbiota samples. To cover the interindividual diversity of gut microbiome composition, fecal samples from ten healthy volunteers were used. Although unchanged levels of most annotated compounds were observed during simulated upper intestinal tract digestion, incubation with fecal microbiota led to a significant change of the chemical profile of the extract. While hyperforins remained stable, flavonoids and hypericins were rapidly biotransformed, suggesting that they may act as prodrugs. Several metabolites were formed, many of which are known to be involved in gut-brain communication. Differential abundance analysis revealed significant changes in microbiome composition, particularly for taxa known to be potentially associated with depression. Among others, the Firmicutes/Bacteroidetes ratio, known to be lowered in depressive patients, was increased. Functional profiling revealed modulation of pathways involved in gut-brain communication, such as tyrosine and tryptophan metabolism. These bidirectional interactions suggest for the first time the gut microbiome as a potential mediator of the pharmacological effects of St. John's wort extracts via the microbiome-gut-brain axis.
-
Correlation between Anxiety, Depression, and Intestinal Flora in Breast Cancer Patients: Based on 16S rRNA Sequence Analysis.
OBJECTIVE: To explore intestinal flora differences in species diversity, community structure, and abundance of breast cancer and non-breast cancer populations with anxiety and depression and the corresponding group without anxiety and depression by 16S rRNA high-throughput sequencing technology. METHOD: Breast cancer and non-breast cancer participants were recruited based on the inclusion and exclusion criteria as the research subjects. The study employed the anxiety self-assessment scale and the depression self-rating scale in the questionnaire survey to collect data. RESULTS: The scores of anxiety and depression of the four groups are as follows: In the breast cancer with anxiety and/or depression (BCAD) group, the anxiety score is 58.80 ± 5.27 and the depression score is 59.60 ± 4.94. In the breast cancer without anxiety and/or depression (BCWAD) group, the anxiety score is 36.53 ± 4.52 and the depression score is 38.20 ± 3.78. In the non-breast cancer group with anxiety and/or depression (HAD) group, the anxiety score is 57.87 ± 4.53 and the depression score is 59.13 ± 5.24. In the non-breast cancer group without anxiety and depression (HWAD) group, the anxiety score is 35.13 ± 5.28 and the depression score is 32.33 ± 4.37. CONCLUSION: The intestinal flora of the breast cancer patients is significantly different from those of non-breast cancer patients, suggesting that there is an internal relationship between the changes in the intestinal flora and the occurrence and development of breast cancer. People with anxiety and depression without breast cancer show changes in their intestinal flora, suggesting that the changes of the intestinal flora can indeed trigger anxiety and depression. For the breast cancer patients with anxiety and depression, the intestinal flora shows a decrease in diversity and abundance, suggesting that the intestinal flora of the breast cancer patients with anxiety and depression undergo further changes. Thus the intestinal flora can become a new tool for monitoring, preventing, and treating the breast cancer and negative emotions.
-
Systems biology approaches to identify potential targets and inhibitors of the intestinal microbiota to treat depression.
Depression is a common mental disease, with some patients exhibiting ideas and behaviors such as self-harm and suicide. The drugs currently used to treat depression have not achieved good results. It has been reported that metabolites produced by intestinal microbiota affect the development of depression. In this study, core targets and core compounds were screened by specific algorithms in the database, and three-dimensional structures of these compounds and proteins were simulated by molecular docking and molecular dynamics software to further study the influence of intestinal microbiota metabolites on the pathogenesis of depression. By analyzing the RMSD gyration radius and RMSF, it was finally determined that NR1H4 had the best binding effect with genistein. Finally, according to Lipinski's five rules, equol, genistein, quercetin and glycocholic acid were identified as effective drugs for the treatment of depression. In conclusion, the intestinal microbiota can affect the development of depression through the metabolites equol, genistein and quercetin, which act on the critical targets of DPP4, CYP3A4, EP300, MGAM and NR1H4.
-
IUPHAR review. Gut microbial metabolites as remote regulators of behavior and neuropsychiatric disease.
The gut-brain axis has emerged as a fundamental pathway through which gut-derived microbial metabolites exert remote control over brain development, neural circuit function and behavior. This Review synthesizes evidence that key microbial metabolites including short-chain fatty acids, tryptophan derivatives, bile acids and trimethylamine N-oxide modulate neuroimmune, neuroendocrine and synaptic signaling in a context-dependent manner, influencing whether the brain maintains homeostasis or progresses toward pathology. We critically evaluate how these metabolites contribute to the etiology and symptomatology of neurodevelopmental and psychiatric disorders such as autism spectrum disorder, major depressive disorder, anxiety and post-traumatic stress disorder. Causal insights are highlighted by studies demonstrating that fecal microbiota transplantation from affected individuals to rodents transfers core behavioral phenotypes. It is important to note, however, that while FMT and gnotobiotic studies establish causality in animal models, evidence from human studies remains predominantly correlative, and we have explicitly distinguished these evidence tiers throughout. We also explore the translational potential of microbiome-derived biomarkers for diagnosis and the challenges in developing targeted therapeutics, including probiotics, postbiotics and metabolite-sequestering agents. Moving forward, the field should prioritize decoding the contextual determinants of microbial influence and adopt personalized, function-based strategies to effectively modulate the gut-brain metabolic axis for brain health.
-
Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.
It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite's effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.Clinical trial NCT00360399 "Predictors of Antidepressant Treatment Response: The Emory CIDAR" https://clinicaltrials.gov/ct2/show/NCT00360399 .
-
Pharmaco-psychiatry and gut microbiome: a systematic review of effects of psychotropic drugs for bipolar disorder.
Despite being one of the most common and debilitating mood disorders, bipolar disorder is often misdiagnosed and undertreated. Its pathogenesis is complex, with significant patient variability and inconsistent treatment effectiveness. The brain-gut-microbiota axis plays a critical role in bipolar disorder by modulating neurotransmitter secretion, gut peptides and systemic inflammation. However, the mechanisms by which psychotropic treatments influence gut microbiota composition and their implications for clinical outcomes remain poorly understood. This systematic review evaluated the impact of psychotropic drugs on gut microbiota and their potential role in bipolar disorder treatment outcomes. A comprehensive search across Ovid MEDLINE, Embase, APA PsycINFO, Scopus and PubMed yielded 314 articles, of which 12 met the inclusion criteria (last search: 13 August 2024). The studies included were those on adults with bipolar disorder type I or II receiving psychopharmacological treatments; those with group comparisons (e.g. healthy controls vs. medicated vs. non-medicated) investigating gut microbiome changes; and no restrictions applied to psychotic features, comorbid anxiety or prior treatment responses. Exclusions involved individual case reports, incomplete conference submissions or early terminated studies lacking efficacy analysis. Cochrane ROBINS-I V2 tool was used to measure the risk of bias, and the GRADE approach was utilized to rate the certainty of evidence in included studies. Two authors independently extracted data into Excel spreadsheets, categorizing demographic and clinical characteristics, describing microbiome analytic methods and summarizing findings on gut microbiome changes post-treatment. Given the high variability in methods and outcome measures across studies, all details were reported without data conversion. Data synthesis reveals that psychotropic treatments, including quetiapine and lithium, influence gut microbiota by increasing the abundance of beneficial bacteria supporting gut health and pathogenic bacteria linked to metabolic dysfunction. Notably, female patients exhibited more significant changes in microbial diversity following psychotropic treatment. Additionally, patients treated with psychotropics showed an increased prevalence of gut bacteria associated with multidrug antibiotic resistance. In bipolar patients treated with quetiapine, responders - those experiencing improved depressive symptom scores - displayed distinct gut microbiome profiles more closely resembling those of healthy individuals compared with non-responders. Responders also exhibited neural connectivity patterns similar to healthy subjects. These findings underscore the complex dual impact of psychotropic medications on gut microbiota, with potential consequences for both gut and mental health. While the enrichment of beneficial bacteria may support gut health, the rise in antibiotic-resistant and metabolically disruptive bacteria is concerning. Study limitations include methodological heterogeneity, inclusions of other psychiatric disorders, a high risk of bias in some studies due to incomplete statistical analyses or insufficient control for confounding factors and potential duplication of study populations arising from overlapping authorship. Further research is essential to elucidate the functional consequences of these microbial shifts and their influence on treatment efficacy. Nevertheless, this review highlights the potential of utilizing gut microbiota profiles to inform personalized treatment strategies, optimize therapeutic outcomes and minimize side effects in bipolar disorder. This study was registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/3GUZR).
-
The Effects of Probiotics on Symptoms of Depression: Protocol for a Double-Blind Randomized Placebo-Controlled Trial.
BACKGROUND: A growing body of evidence has linked mental health outcomes to the gut microbiome. This has led to the investigation of the GI tract as a target for novel treatments and interventions for depression, including probiotic supplementation. Our recent pilot study provided the first evidence of probiotics improving symptoms of depression in treatment-naive depressed patients. To further support and expand upon this evidence, data from the pilot study were used to plan a 16-week, double-blind, randomized, placebo-controlled trial to assess the effects of probiotics on depression. Here, we report the protocol for this trial. METHODS: Participants diagnosed with depression will orally consume a probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum or placebo once daily. Participants will undergo assessments measuring clinical outcomes using a battery of validated clinical scales and questionnaires. Sleep architecture and quality will be measured using polysomnography. Neuroimaging data will be collected using magnetic resonance imaging to examine functional and structural neurophysiological changes. Molecular data will be collected from blood, stool, and urine samples to examine cytokine levels and explore potential genes and proteins that may predict outcomes in depression. RESULTS: We expect results to replicate and expand on our pilot data demonstrating that probiotics may be effective in alleviating symptoms of depression, and to find biomarkers that will predict these outcomes. CONCLUSIONS: The findings from this study will add to the growing body of research in this emerging field, which eventually may provide evidence for probiotics having a role in alleviating symptoms of depression.
-
A Study of the Relationship between Inflammatory Immune Function and Intestinal Flora in Adolescent Patients with First-Episode Depression.
BACKGROUND: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. METHODS: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. RESULTS: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1β, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). Bifidobacterium, Escherichia coli, Lactobacillus, and Bacteroides in the observation group were less than those in the control group (p < 0.05). The content of Bifidobacterium was negatively correlated with the level of TNF-α (r = -0.358, p < 0.001), positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = 0.490, 0.169, 0.165, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.154, p < 0.05). The level of Escherichia coli content was negatively correlated with the levels of IL-6, CD3+, CD4+, CD4+/CD8+ (r = -0.483, -0.548, -0.317, -0.328, p < 0.001), and positively correlated with the levels of CD8+ (r = 0.325, p < 0.001). The content of Lactobacillus was positively correlated with the levels of CD3+, CD4+, CD4+/CD8+ (r = 0.552, 0.188, 0.194, p < 0.05), and negatively correlated with the level of CD8+ (r = -0.186, p < 0.05). The content of Bacteroides was positively correlated with the level of CD3+, CD4+, CD4+/CD8+ (r = -0.570, -0.183, -0.193, p < 0.05), and negatively correlated with the level of CD8+ levels were positively correlated (r = 0.187, p < 0.05). CONCLUSIONS: The intestinal flora is related to the level of inflammatory factors and immune function. Further study on the relationship between intestinal flora, inflammatory immune function, and depression could offer novel insights for the prevention and treatment of depressive disorders.
-
Chronic psilocybin administration increases sociability and alters the gut microbiome in male wild-type mice but not in a preclinical model of obsessive-compulsive disorder.
Psilocybin, a serotonergic compound that produces psychedelic effects primarily through activation of the 5-HT2A receptor, has shown promise in treating neuropsychiatric conditions, including obsessive-compulsive disorder (OCD). However, the effects of chronic psilocybin administration on gut function, microbiota, and behavioural phenotypes remain understudied. The present study investigated the effects of chronic psilocybin (0.1 and 1 mg/kg, oral gavage) on gut and behavioural measures in wild-type (WT) and SAPAP3 knockout (KO) mice, a model of OCD-like phenotypes. We present novel evidence that SAPAP3 KO mice exhibit social deficits, and that chronic psilocybin increases sociability in male WT mice. Although no therapeutic effects were observed at either dose on anxiety-, compulsive-, or depressive-like behaviour, chronic psilocybin also did not induce psychosis-like behaviours. A dose-dependent effect of psilocybin was observed on gut motility. Although chronic administration did not significantly alter overall gut microbiome diversity, reductions in Lactobacillus murinus, Lactobacillus animalis, and Alistipes dispar were observed in male WT mice, but not in KO mice or female mice. Integrative analysis revealed that a microbial cluster, comprising Lactobacillus and Alistipes species, correlated with locomotion, head-twitch response and gut motility, effectively differentiating psilocybin-treated mice from vehicle controls. This suggests a potential host-microbiome feedback mechanism regulating host serotonin signalling, linked to central and peripheral 5-HT2A receptor activation. Additionally, separate microbial clusters were associated with startle response and sociability, indicating that psilocybin may engage distinct neural pathways to mediate these behaviours. These findings highlight the importance of considering the microbiome and sex in future psychedelic research and open new avenues for exploring the microbiota-gut-brain axis as a target for future therapeutic strategies.