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: 3 198
Page 58 of 320-
CD36 deficiency affects depressive-like behaviors possibly by modifying gut microbiota and the inflammasome pathway in mice.
Both inflammatory processes and gut microbiota have been implicated in the pathophysiology of depressive disorders. The class B scavenger receptor CD36 is involved in the cytotoxicity associated with inflammation. However, its role in depression has not yet been examined. In this study, we investigated whether CD36 affects depression by modulating the microbiota-gut-inflammasome-brain axis. We used CD36-/- (knockout) mice subjected to chronic social defeat stress, and measured the expression of CD36 in these depressed mice and in patients with depression. The hippocampus of CD36-/- mice was used to investigate changes in the NLRP3 inflammasome signaling pathway. The 16S rRNA gene sequence-based approach was used to compare the cecal microbial communities in CD36-/- and WT mice. The CD36 deficiency in CD36-/- mice alleviated chronic stress-induced depression-like behaviors. CD36 was upregulated in depressed mice as well as in depressed patients. Furthermore, the NLRP3 inflammasome signaling pathway was downregulated in the hippocampus of CD36-/- mice. The Simpson Diversity Index revealed increased cecal bacterial alpha-diversity in the CD36-/- mice. Among genera, Bacteroides, Rikenella, and Alloprevotella were significantly more abundant in the CD36-/- mice, whereas Allobaculum was less abundant, consistent with the attenuated inflammation in the hippocampus of CD36-/- mice. Our findings suggest that CD36 deficiency changes the gut microbiota composition, which in turn may impact depressive-like behaviors by affecting the inflammasome pathway.
-
The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.
BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology. RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety. CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.
-
The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study.
BACKGROUNDS: The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. METHODS: We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. RESULTS: At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. LIMITATIONS: The small sample size with no control group. CONCLUSIONS: Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.
-
Puerarin Alleviates Depression via Integrated Regulation of TLR4/MyD88/NF-κB Signaling and Gut Microbiota-Metabolic Axis.
Depression is a highly prevalent mental disorder in which dysfunction of the gut microbiota is implicated as a significant factor in its pathogenesis. Puerarin has been suggested to alleviate depression via the microbe-gut-brain axis (MGBA), although the precise mechanisms remain elusive. This study aimed to elucidate the association between the antidepressant effects of puerarin and its role in regulating intestinal flora imbalance and inhibiting subsequent activation of the LPS/TLR4 inflammatory pathway from metabolomics and metagenomics perspectives. A rat model of depression was established using a 6-week chronic unpredictable mild stress (CUMS) protocol. Depressive-like behaviors were assessed through the sucrose preference test (SPT), forced swim test (FST), and open field test (OFT). Inflammatory cytokines (TNF-α, IL-1β, IL-6), LPS, corticosterone, and 5-HT were measured via ELISA. Hippocampal and colonic protein expression of TLR4, MyD88, IκBα, and NF-κB was analyzed by western blot. Colon tissue integrity was evaluated using H&E staining, PAS staining, and transmission electron microscopy. Immunofluorescence was employed to detect Iba-1+ microglia, TLR4+ cells, and ZO-1 expression. Fecal metabolomics and metagenomics were conducted to identify differential metabolites and microbial composition, followed by KEGG and KO enrichment analyses to predict relevant pathways. Spearman correlation analysis was used to explore relationships among gut microbiota, metabolites, and behavioral indices. Puerarin markedly ameliorated depression-like behaviors in CUMS rats. Concurrently, puerarin inhibited the LPS/TLR4 signaling pathway and its downstream pro-inflammatory mediators in both the hippocampus and colon, resulting in a significant reduction in inflammatory responses across these regions, as well as in the serum. Metagenomic sequencing revealed that puerarin suppressed inflammation-associated bacteria, enhanced the abundance of Firmicutes, and induced alterations in the microbial community structure and composition. Metabolomic analysis demonstrated that puerarin could counteract dysregulated fecal metabolism, identifying 17 metabolites as potential key mediators in restoring metabolic homeostasis in CUMS rats. These biomarkers were implicated in several metabolic pathways, including Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, Alanine, Aspartate, and Glutamate metabolism. Puerarin may exert its antidepressant effects by modulating the gut microbial structure and metabolite profiles, thereby alleviating inflammatory stress in the colon, bloodstream, and hippocampus, potentially through inhibition of the LPS/TLR4 signaling pathway.
-
Gut microbiome and glial cell dialog: Role of TCM in the treatment of depression.
BACKGROUND: Depression is characterized by low mood, cognitive slowing and a tendency to self-harm, and has a complex etiology involving abnormalities in neuromodulation (e.g., monoamine transmitter imbalance and reduced neuroplasticity). Gut-brain axis studies have shown that dysregulation of gut flora can trigger neuroinflammation and impair glial cell function, leading to depression. Modulation of flora-glial cell interactions and their pharmacological mechanisms is key to treatment. PURPOSE: This review discusses the new discovery of the interaction mechanism between glial cells and gut microflora in depression models, providing new targets and directions for the treatment of TCM in depression. Further bridging the gap in current research on the gut-brain axis in depression. METHOD: Literature was searched, analyzed, and collected using PubMed, Web of Science, and China National Knowledge Infrastructure. The search terms used were " gut-brain axis ", " neuroinflammation ", " depression ", " glial cells ", " Gut microbiota "," TCM ", etc. Several combinations of these keywords were used. Studies using models of depression were used. RESULTS: During the literature screening process, a total of 1685 records were initially retrieved from databases. After removing duplicates (1068) and other ineligible records (200), 417 articles underwent title and abstract screening, with 134 excluded. Further full-text assessment of 283 articles led to the inclusion of 149 new studies. Reasons for exclusion included mismatched outcomes (8), ineligible experimental models (12), among others. Combined with 14 previously included studies, the final review comprised 163 articles (See Figure 1). The dialog mechanism between gut microflora and glial cells plays an important role in the pathogenesis of depression. In addition, there are a variety of herbal active ingredients and herbal formulas that can significantly affect the composition of the gut flora and glial cell activation in depression models, and consequently, there is significant antidepressant potential. CONCLUSION: Intestinal flora metabolites modulate glial cell activation, and the release of inflammatory factors by glial cells alters intestinal flora composition, both phenomena are contributory to depressive pathogenesis. In addition, we found that a variety of TCMs can improve depression based on this mechanism, providing new perspectives for clinical diagnosis and treatment of depression.
-
Hirami lemon (Citrus reticulata var. depressa) modulates the gut-brain axis in a chronic mild stress-induced depression mouse model.
Citrus reticulata var. depressa, commonly known as Hirami lemon, is a native citrus species found in Taiwan and Okinawa islands of Japan. While several Citrus species are known to possess antidepressant activity by modulating the gut microbiota, the antidepressant effect of Hirami lemon and its underlying mechanisms have not been thoroughly investigated. In this study, we explored the potential antidepressant efficacy of the fruit extract (CD) and the essential oil (CDE) from Hirami lemon peel using a chronic mild stress (CMS)-induced mouse model and analyzed the association of gut microbiome changes. Our findings revealed that mice subjected to CMS exhibited anxiety- and depression-like behaviors as assessed by elevated plus-maze and forced swimming tests, respectively. Significantly, oral administration of CDE and CD notably reversed CMS-induced depression- and anxiety-like behaviors in CMS-induced mice. Moreover, compared to the non-stressed group, CMS significantly altered the gut microbiome, characterized by highly diverse bacterial communities, reduced Bacteroidetes, and increased Firmicutes. However, oral administration of CDE and CD restored gut microbiota dysbiosis. We also performed a qualitative analysis of CD and CDE using UPLC-MS and GC-MS, respectively. The CD contained 25 compounds, of which 3 were polymethoxy flavones and flavanones. Three major compounds, nobiletin, tangeretin and hesperidin, accounted for 56.88% of the total relative peak area. In contrast, the CDE contained 11 terpenoids, of which 8 were identified as major compounds, with D-limonene (45.71%) being the most abundant, followed by γ-terpinene (34.65%), linalool (6.46%), p-cymene (2.57%), α-terpineol (2.04%), α-pinene (1.89%), α-terpinolene (1.46%), and β-pinene (1.16%), accounting for 95.94% of the total oil. In conclusion, our study demonstrated the potential of Hirami lemon as a source of natural antidepressant agents for the prevention and treatment of major depressive disorders.
-
The potential of food-derived peptides in alleviating depressed mood: Function, evaluation and mechanism.
Food-derived peptides offer a promising approach to alleviating depressive symptoms due to their safety and natural origin, avoiding the adverse side effects of conventional pharmacological treatments. This review aims to explore their potential in mitigating depressive symptoms. Antidepressant peptides from both animal and plant sources have been reviewed, while the animal models and evaluation methods used to assess their efficacy have been summarized. The review highlights four major mechanisms underlying their effects, namely modulation of gut microbiota and production of neuroactive metabolites, alteration of molecules associated with nervous system, normalization of hypothalamic-pituitary-adrenal axis dysregulation to reduce cortisol production, and suppression of pro-inflammatory cytokines linked to neuroinflammation. It also highlights the role of gut-brain axis in mediating the mechanisms, which has been insufficiently elucidated. However, the efficacy of antidepressant peptides for clinical use has not been established. The present review provides a reference for developing dietary interventions with food-derived peptides to supplement current therapeutic approaches.
-
Probiotic treatment rescues behavioral deficits and gut microbial abnormalities induced by preconceptional stress in mothers and offspring.
Depression and anxiety during pregnancy are major public health concerns with lasting consequences for mother and child. Although the gut microbiome contributes to stress and mood regulation, its role in preconceptional stress and transgenerational outcomes remains unclear. Here, we examined behavioral, microbial, and thalamic transcriptional effects of preconceptional social isolation rearing (SIR) in female mice and tested whether maternal probiotic supplementation mitigates these alterations. SIR females displayed increased anxiety-like and social-avoidant behavior, reduced gut microbial diversity, depletion of Odoribacter, Tuzzerella, and Alloprevotella, and enrichment of Bacteroides and Lachnospiraceae. A multispecies probiotic (Lactobacillus rhamnosus HN001, L. acidophilus La-14, Bifidobacterium lactis HN019) reversed these behavioral and microbial changes. Adult offspring of SIR dams showed sex-dependent behavioral deficits and microbial alterations partly reflecting maternal patterns. Prenatal SIR was associated with reduced thalamic Bdnf expression in offspring and altered Grin2a/2b selectively in males. In contrast, prenatal probiotic exposure exerted broader transcriptional effects and restored Bdnf levels in SIR offspring. SIR-induced increases in Lachnospiraceae were transmitted to offspring, whereas reductions in Ruminococcaceae were normalized by maternal probiotic treatment. Predicted functional profiling indicated sex-dependent modulation of microbial pathways related to tryptophan and central carbon metabolism. These findings demonstrate enduring transgenerational effects of preconceptional stress on the gut-brain axis and support maternal probiotic supplementation as a potential strategy to mitigate stress-induced dysregulation.
-
Oral coniferyl ferulate attenuated depression symptoms in mice via reshaping gut microbiota and microbial metabolism.
The gut microbiome is known to be involved in depression development. Thus, phytochemicals changing gut microbiota may alleviate depression-like behaviors. Coniferyl ferulate (CF) is a long studied natural product and known to alleviate psychiatric disorders. However, its mechanism of action remains unclear. In this experimental study, oral administration of 50 mg kg-1 CF once daily attenuated weight loss and depression-like and anxiety-like behaviors induced by chronic unpredicted mild stress (CUMS) in mice. Four weeks of CF administration significantly ameliorated colonic inflammation, lowered the levels of IL-6, IL-1β, and TNF-α, and restructured the gut microbiome, and microbial metabolism. Intestinal microbiota can impact the development and function of the brain via the microbiota-gut-brain axis. Therefore, oral administration of CF is a promising nutritional strategy to treat CUMS-induced depression via the regulation of microbiota and microbial metabolism.
-
Gut microbiota causes depressive phenotype by modulating glycerophospholipid and sphingolipid metabolism via the gut-brain axis.
Emerging evidence suggests that changes in the gut microbiota (GM) are related to prenatal depression onset, but the underlying molecular mechanisms remain obscure. This study was conducted to explore how disordered GM is involved in the onset of prenatal depression through the microbiome-gut-brain (MGB) axis. We transplanted fecal microbiota from women with and without prenatal depression into germ-free mice. Fecal metagenomic sequencing and LC-MS untargeted metabolomics analysis were performed to identify the GM composition, function, and metabolites in mice. Lipid metabolomics analysis was then used to characterize the lipid metabolism of brain tissue in mice. We found that mice transplanted with fecal microbiota from women with prenatal depression exhibited depressive-like behaviors as well as characteristic disorders of the phylum Firmicutes. Weighted Gene Correlation Network Analysis identified three microbial and one metabolic module in the gut, alongside two lipid metabolic modules in the brain, as significantly related to all depressive-like behaviors. These modules were enriched for glycerophospholipid and sphingolipid metabolism. In addition, the GM of mice with depressive-like behaviors were enriched and deficient in relevant functions and enzymes in the glycerophospholipid (mainly phosphatidylethanolamine) and sphingolipid (mainly hexosyl-ceramide) metabolic pathways, respectively. Consistently, glycerophospholipid and sphingolipid metabolites in the brains of depressive-like mice were up- and down-regulated. Increased phosphatidylethanolamine and decreased hexosyl-ceramide were significantly related to differential genera in the gut. Collectively, our findings provide a novel microbial and metabolic framework for understanding the role of the MGB axis in prenatal depression, indicating that the GM may be involved in the onset of depressive phenotypes by modulating central glycerophospholipid and sphingolipid metabolic homeostasis.