Brain-Immune system-Gut Interaction in Chronic Mild Stress (CMS +/- Lacto)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
TISSUE(S): Unspecified
DISEASE(S): Stress
PROVIDER: ST000696 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
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Project description:BackgroundMajor depressive disorder is a leading cause of disability worldwide, affecting up to 17 % of the general population. The neural mechanisms of depression, however, are yet to be uncovered. Recently, attention has been drawn to the effects of dysfunctional brain-gut axis on depression, and many substances have been suggested to be involved in the communication between the gut and brain, such as ghrelin.MethodsWe herein systematically examined the changes of metabolomics after unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in rats and compared the altered metabolites in the hippocampus and jejunum samples.ResultsOur results show that many metabolites significantly changed with UCMS both in the hippocampus and jejunum, such as L-glutamine, L-tyrosine, hydroxylamine, and 3-phosphoglyceric acid. Further studies suggested that these changes are the reasons for anxiety-like behaviors and depression-like behaviors in UCMS rats and also are the reasons for hippocampal neural plasticity.ConclusionsCoexistence of brain and gut metabolic changes in UCMS-induced depressive behavior in rats suggests a possible role of brain-gut axis in depression. This study provides insights into the neurobiology of depression.
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Project description:RationaleThe involvement of somatostatin (SST) and its receptors in the pathophysiology of depression and stress has been evidenced by numerous studies.ObjectivesThe purpose of the present study was to find whether chronic mild stress (CMS), an animal model of depression, affects the SST receptors in the rat brain and pituitary, as well as the level of SST in plasma.MethodsIn CMS model, rats were subjected to 2 weeks of stress and behaviorally characterized using the sucrose consumption test into differently reacting groups based on their response to stress, i.e., stress-reactive (anhedonic), stress-non-reactive (resilient), and invert-reactive rats (characterized by excessive sucrose intake). We measured specific binding of [125I]Tyr3-Octreotide, expression of mRNA encoding sst2R receptors in the rat brains, expression of SST and its receptors in rat pituitary, and the level of SST in the plasma.ResultsThe obtained results show decreases in binding of [125I]Tyr3-Octreotide in most of rat brain regions upon CMS and no significant differences between three stressed groups of animals, except for significant up-regulation of sst2 receptor in medial habenula (MHb) in the stress-reactive group. In the same group of animals, significant increase in plasma SST level was observed.ConclusionsThere are two particularly sensitive sites distinguishing the response to stress in CMS model. In the brain, it is MHb, while on the periphery this predictor is SST level in plasma. These changes may broaden an understanding of the mechanisms involved in the stress response and point to the intriguing role of MHb.
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Project description:Chronic stress is known to perturb serotonergic regulation in the brain, leading to mood, learning and memory impairments and increasing the risk of developing mood disorders. The influence of the gut microbiota on serotonergic regulation in the brain has received increased attention recently, justifying the investigation of the role of diet on the gut and the brain in mood disorders. Here, using a 4-week chronic unpredictable mild stress (CUMS) model in mice, we aimed to investigate the effects of a high-fat high-glycaemic index (HFD) and high-fibre fruit & vegetable "superfood" (SUP) modifications of a semi-pure AIN93M diet on behaviour, serotonin synthesis and metabolism pathway regulation in the brain and the gut, as well as the gut microbiota and the peripheral adrenal medullary system. CUMS induced anxiety-like behaviour, dysregulated the tryptophan and serotonin metabolic pathways in the hippocampus, prefrontal cortex, and colon, and altered the composition of the gut microbiota. CUMS reduced the catecholamine synthetic capacity of the adrenal glands. Differential effects were found in these parameters in the HFD and SUP diet. Thus, dietary modifications may profoundly affect the multiple dynamic systems involved in mood disorders.
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Project description:ObjectivesSunflower seeds provide tryptophan-rich proteins with the potential to protect against depression. Tryptophan is a precursor of serotonin and a substrate for the production of indole derivatives by gut microbiota. This study aimed to investigate the association between the depression-alleviating effects of deoiled and dechlorogenic sunflower seeds (DSFS) and regulation of gut microbiota.Materials and methodsMale C57BL/6J mice were fed a diet comprising a source of soy protein (normal and model control), DSFS or whey protein concentrate (positive control) for 7 weeks, and chronic stress-induced depression was induced.ResultsFeeding the DSFS diet prevented depression-like behaviors, intestinal barrier damage, elevated plasma corticosterone, and reduced hippocampal serotonin levels in mice. Meanwhile, Feeding the DSFS diet significantly altered the gut microbiota structure, characterized by elevated relative abundances of Ileibacterium valens, Ruminococcus flavefaciens, Clostridium scindens, and Olsenella massiliensis, which were inversely associated with depressive behaviors and markers of mucosal barrier damage. DSFS also altered the gut metabolite profile, prevented depression-induced gut L-tryptophan depletion, and upregulated its metabolite indoleacetaldehyde.ConclusionFeeding the DSFS diet prevented depression in mice by remodeling the gut microbiota and bacterial tryptophan metabolism.
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Project description:A growing body of evidence suggests that gut microbiota could participate in the progression of depression via the microbiota-gut-brain axis. However, the detailed microbial metabolic profile changes in the progression of depression is still not fully elucidated. In this study, a liquid chromatography coupled to mass spectrometry-based untargeted serum high-throughput metabolomics method was first performed to screen for potential biomarkers in a depressive-like state in a chronic unpredictable mild stress (CUMS)-induced mouse model. Our results identified that the bile acid and energy metabolism pathways were significantly affected in CUMS progression. The detailed bile acid profiles were subsequently quantified in the serum, liver, and feces. The results showed that CUMS significantly promoted the deconjugation of conjugated bile acid and secondary bile acid biosynthesis. Furthermore, 16S rRNA gene sequencing revealed that the increased secondary bile acid levels in the feces positively correlated with Ruminococcaceae_UCG-010, Ruminococcus, and Clostridia_UCG-014 abundance. Taken together, our study suggested that changes in family Ruminococcaceae abundance following chronic stress increased biosynthesis of deoxycholic acid (DCA), a unconjugated secondary bile acid in the intestine. Aberrant activation of secondary bile acid biosynthesis pathway thereby increased the hydrophobicity of the bile acid pool, which might, in turn, promoted metabolic disturbances and disease progression in CUMS mice.
| S-EPMC8936594 | biostudies-literature
Project description:Dysbiosis of the gut microbiota is associated with the development of depression, but the underlying mechanism remains unclear. The aim of this study was to determine the relationship between microbiota and NLRP3 inflammasome induced by chronic unpredictable mild stress (CUMS). Fecal transplantation (FMT) experiment was conducted to elucidate the potential mechanism. Levels of NLRP3 inflammasome, microbiota, inflammatory factors and tight junction proteins were measured. CUMS stimulation significantly increased the levels of NLRP3, Caspase-1 and ASC in brain and colon(p<0.05), decreased the levels of tight junction proteins Occludin and ZO-1 (p<0.05). Interestingly, increased NLRP3 inflammasome and inflammatory cytokines and decreased tight junction proteins were found in antibiotic-treated (Abx) rats received CUMS rat fecal microbiota transplantation. Furthermore, fecal microbiota transplantation altered the microbiota in Abx rats, which partially overlapped with that of the donor rats. Importantly, probiotic administration amended the alteration of microbiota induced by CUMS treatment, then reduced the levels of NLRP3 inflammasome and inflammatory factors. In conclusion, these findings suggested that depression-like behaviors induced by CUMS stimulation were related to altered gut microbiota, broke the intestinal barrier, promoted the expression of NLRP3 inflammasome and elevated inflammation. Therefore, improving the composition of microbiota via probiotic can attenuate inflammation by amending the microbiota and suppressing the activation of NLRP3 inflammasome, which is considered as a novel therapeutic strategy for depression.
| S-EPMC10244772 | biostudies-literature
Project description:IntroductionSeveral studies indicated that depression is associated with liver injury. The role of probiotics in alleviating depression is focused on improving the abnormalities of the central nervous system through the gut-brain axis, while the effect on liver injury is still unclear. The aim of this study was to elucidate the potential link between the antidepressant effect of a potential probiotic strain Bifidobacterium pseudocatenulatum W112 and its effect on alleviating liver injury.MethodsThe 4-week-old Kunming mice were exposed to chronic stress for 4 weeks to establish a depression model.ResultsThe depression-like behavior and related biomakers in chronic unpredictable mild stress (CUMS) mice were altered by supplemented with W112 for 2 weeks. Meanwhile, the modulation effect of W112 the gut microbiota in CUMS mice also result in an increase in the abundance of beneficial bacteria and a decrease in the abundance of harmful bacteria. Significantly, liver injury was observed in CUMS model mice. W112 improved liver injury by reducing AST/ALT in serum. Quantitative PCR results indicated that the mechanism of action of W112 in ameliorating liver injury was that the altered gut microbiota affected hepatic phospholipid metabolism and bile acid metabolism.DiscussionIn short, W112 could significantly improve the depressive and liver injury symptoms caused by CUMS. The gut-liver-brain axis is a potential connecting pathway between the antidepressant effects of W112 and its alleviation of liver injury.
| S-EPMC11366711 | biostudies-literature
Project description:Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.
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Project description:The severe harm of depression to human life has attracted great attention to neurologists, but its pathogenesis is extremely complicated and has not yet been fully elaborated. Here, we provided a new strategy for revealing the specific pathways of abnormal brain glucose catabolism in depression, which from the supply of energy substrates and the evaluation of mitochondrial structure and function. By using stable isotope-resolved metabolomics technique, we discovered the tricarboxylic acid cycle (TCA cycle) is blocked and the gluconeogenesis is abnormally activated in chronic unpredictable mild stress (CUMS) rats. In addition, our results showed an interesting phenomenon that the brain attempted to activate all possible metabolic enzymes in energy-producing pathways, but CUMS rats still exhibited a low TCA cycle activity due to impaired mitochondria. Depression caused mitochondrial structure and function impaired, and then led to abnormal brain glucose catabolism. The combination of the stable isotope-resolved metabolomics and mitochondrial structure and function analysis can accurately clarify the mechanism of depression. The mitochondrial pyruvate carrier and acetyl-CoA maybe the key targets for depression treatment. The strategy provides a unique insight for exploring the mechanism of depression, the discovery of new targets, and the development of ideal novel antidepressants.
2021-06-10 | PXD025548 | Pride
Project description:The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.
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