Neuropeptide SP protects against colitis and linked anxiety-like behavior via gut microbiota and metabolite inositol: A multi-omics analysis of the gut-brain axis
Ontology highlight
ABSTRACT: The gut-brain axis facilitates two-way communication between gut inflammation and psychiatric comorbidities associated with inflammatory bowel disease (IBD). In this study, we examined the neuroprotective effects of the neuropeptide substance P (SP) on colitis. Taking into account the interactions between the intestinal microbiota and host metabolism, along with the influence of microbiota-derived metabolites on gut-brain signaling, we conducted an untargeted metabolomic analysis.
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase
PROVIDER: MTBLS11203 | MetaboLights | 2025-11-18
REPOSITORIES: MetaboLights
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| AX112-ZX01-0101-neg-QC-1.raw | Raw | |||
| AX112-ZX01-0101-neg-QC-2.raw | Raw | |||
| AX112-ZX01-0101-neg-QC-3.raw | Raw | |||
| AX112-ZX01-0101-neg-QC-4.raw | Raw | |||
| AX112-ZX01-0101-neg-QC-5.raw | Raw |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:Gut-microbiota membership is associated with diverse neuropsychological-diseases, including substance use disorders (SUDs). Unravelling mechanistic interactions between gut microbes and the host during psychostimulant use remains challenging. Here we show that cocaine exposure increases intestinal levels of norepinephrine, sensed through the bacterial adrenergic receptor QseC, promoting intestinal colonization of g-Proteobacteria. Gut colonization by g-Proteobacteria depletes the neuroactive metabolite glycine (used as a nitrogen source) both in the gut and cerebrospinal fluid, enhancing host cocaine-induced behaviors. Glycine repletion reversed this response, and intestinal colonization by g-Proteobacteria unable to uptake glycine did not alter the host response to cocaine. Transcriptomic profiling indicates a role of g-Proteobacteria modulated glycine levels in cocaine induced transcriptional plasticity in the nucleus accumbens through the glutamatergic transmission. Altogether, we introduce a mechanism by which intestinal bacteria alter the host’s brain responses to cocaine that could be exploited to modulate reward-related brain circuits that contribute to SUDs.
2022-09-07 | GSE212421 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral/lateral (BLA), the medial (MeA) and central amygdala (CeA), the nucleus accumbens (NAc), the cingulate cortex (Cg) and the supraoptic nucleus (SON) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB and LAB mice. Analysis was performed from six animals per line (HAB and LAB, respectively) pooled per brain region in ten technical replicates, thereof five with a dye-swapped design giving a total of 70 array slides analyzed. The LAB mouse line is referred to as reference.
2011-08-29 | E-GEOD-28999 | biostudies-arrayexpress
Project description:The molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmannâ??s Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness. Keywords: strain difference, genetic variation Microarray Affymetrix GeneChip: From three independent pools (3 hippocampi /pool) of total RNA for each line, probe was labeled, hybridized as one pool per GeneChip, using a total of six mouse MOE 430 arrays (Affymetrix, Santa Clara, CA). The sequential steps of reverse transcriptions, purification of ds cDNA, in vitro transcription and labeling of cRNA with biotin (Enzo BioArray High Yield RNA Transcript Labeling Kit), fragmentation of cRNA, hybridization to gene chips in a Affymetrix fluidics station 400 system, staining with streptavidin-phycoerythrin, washings, and scannings with a GeneArray Scanner were performed as described in the detailed protocols of the Affymetrix GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA) by the UTSW Microarray Core. The Affymetrix two GeneChip MOE 430 A and B set contains more than 45,000 probe sets, interrogating the expression level of 34,000 mouse gene transcripts. Illumina Microarray For the P0.5 microarray study, total RNA from a whole brain was individually used per Sentrix Mouse-6 BeadChip (Illumina, San Diego, CA), allowing individual samples to be evaluated and an increased sample size, namely six P0.5 mouse brains for each of three lines (A/J, B6, A.B6chr10). The Sentrix Mouse-6 BeadChip contains total 47,769 gene-specific, 70-mer oligonucleotide probes. Total RNA from each brain tissue of P0.5 mice was extracted in Trizol as above, reverse transcribed, labeled, and hybridized with a microarray according to the manufacturerâ??s detailed protocol (Illumina, San Diego, Ca.). Briefly, total RNA was reverse transcribed, then in vitro transcribed to cRNA and labeled with biotin-16-UTP. The labeled probe was hybridized to Illumina's Sentrix mouse-6 Expression BeadChips (Illumina, San Diego, CA), washed, and scanned with Illumina's BeadStation 500GX Genetic Analysis System in the UTSW Microarray core.
2010-05-25 | E-GEOD-8641 | biostudies-arrayexpress
Project description:<p>Radiofrequency radiation (RFR) with specific parameters could alter brain function, yet the underlying mechanisms remain unclear. The gut-brain axis is reported to be important in regulating brain function. Therefore, this study used gut microbiota intervention, regulation of tryptophan metabolite and other methods to explore the effect of the gut-brain axis in brain function changes caused by RFR. It was found that 4.9 GHz (a commonly used frequency of 5G) RFR exposure 35 d induced anxiety-like behaviors in mice, accompanied by gut microbiota dysbiosis, tryptophan metabolites imbalance and neuronal pyroptosis. Intervention of intestinal flora through probiotics alleviated RFR-induced anxiety-like behaviors, improved tryptophan metabolism in the brain and reduced neuronal pyroptosis in the medial prefrontal cortex (mPFC). Furthermore, elevating the levels of tryptophan metabolism 5-hydroxytryptamine (5-HT, a key molecule for regulating anxiety) in brain through the administration of the selective serotonin reuptake inhibitor (SSRI) paroxetine ameliorated RFR-induced anxiety-like behaviors and NLRP3 inflammasome-mediated neuronal pyroptosis in the mPFC. This study reveals that RFR can induce gut microbiota dysbiosis, tryptophan metabolism imbalance of gut-brain axis, subsequent neuronal damage in the mPFC and ultimately anxiety-like behaviors in mice. These findings provide novel insights into the mechanism of RFR-induced brain function disorders.</p>
2025-09-12 | MTBLS12482 | MetaboLights
Project description:<p>Radiofrequency radiation (RFR) with specific parameters could alter brain function, yet the underlying mechanisms remain unclear. The gut-brain axis is reported to be important in regulating brain function. Therefore, this study used gut microbiota intervention, regulation of tryptophan metabolite and other methods to explore the effect of the gut-brain axis in brain function changes caused by RFR. It was found that 4.9 GHz (a commonly used frequency of 5G) RFR exposure 35 d induced anxiety-like behaviors in mice, accompanied by gut microbiota dysbiosis, tryptophan metabolites imbalance and neuronal pyroptosis. Intervention of intestinal flora through probiotics alleviated RFR-induced anxiety-like behaviors, improved tryptophan metabolism in the brain and reduced neuronal pyroptosis in the medial prefrontal cortex (mPFC). Furthermore, elevating the levels of tryptophan metabolism 5-hydroxytryptamine (5-HT, a key molecule for regulating anxiety) in brain through the administration of the selective serotonin reuptake inhibitor (SSRI) paroxetine ameliorated RFR-induced anxiety-like behaviors and NLRP3 inflammasome-mediated neuronal pyroptosis in the mPFC. This study reveals that RFR can induce gut microbiota dysbiosis, tryptophan metabolism imbalance of gut-brain axis, subsequent neuronal damage in the mPFC and ultimately anxiety-like behaviors in mice. These findings provide novel insights into the mechanism of RFR-induced brain function disorders.</p>
2025-09-12 | MTBLS12483 | MetaboLights
Project description:TET3 is a member of the Ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult post-mitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes (IEGs) was observed in both dorsal and ventral hippocampal areas. Additionally, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations, that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of psychiatric disorders.
2020-01-16 | GSE140850 | GEO
Project description:Investigating the molecular basis and correlates of anxiety-related and depression-like behaviors, we generated a mouse model consisting of high (HAB), normal (NAB) and low (LAB) anxiety-related behavior mice. We utilized the elevated plus-maze for testing the genetic predisposition to anxiety-related behavior and, consequently, used this as selection criterion for the inbreeding of our animals. In depression-related tests, HAB mice display a more passive, depression-like coping strategy than LAB mice, resembling clinical comorbidity of anxiety and depression as observed in psychiatric patients. Using a microarray approach, the hypothalamic paraventricular nucleus (PVN), the basolateral (BLA) and central amygdala (CeA), the cingulate cortex (Cg) and the dentate gyrus (DG) – centers of the central nervous anxiety and fear circuitries – were investigated and screened for differences between HAB, NAB and LAB mice. Analysis was performed from four to six animals per line (HAB, NAB and LAB from generation 25, respectively) per brain region, giving a total of 78 individual arrays analyzed. The LAB mouse line is referred to as reference.
2011-05-04 | E-GEOD-29014 | biostudies-arrayexpress
Project description:Cocaine use disorder is a condition that leads to tremendous morbidity and mortality for which there are currently no FDA-approved pharmacotherapies. Previous research has demonstrated an important role for the resident population of bacteria of the large intestine, collectively dubbed the gut microbiome, in modulating brain and behavior in models of cocaine and other substance use disorders. Importantly, previous work has repeatedly shown that depletion of the gut microbiome leads to increased cocaine taking and seeking behaviors in multiple models. While the precise mechanism of these gut-brain signaling pathways in models of cocaine use is not fully clear, and intriguing possibility is through gut microbiome influences on innate immune system function. In this manuscript we identify the cytokine colony stimulating factor 2 (CSF2) as an immune factor that is increased by cocaine in a gut microbiome dependent manner. Peripherally injected CSF2 crosses the blood-brain barrier into the nucleus accumbens, a brain region central to behavioral responses to cocaine. Treatment with peripheral CSF2 reduces acute and sensitized locomotor responses to cocaine as well as reducing cocaine place preference at high doses. On a molecular level, we find that peripheral injections of CSF2 alter the transcriptional response to both acute and repeated cocaine in the nucleus accumbens. Finally, treatment of microbiome depleted mice with CSF2 reverses the behavioral effects of microbiome depletion on the conditioned place preference assay. Taken together, this work identifies an innate immune factor that represents a novel gut-brain signaling cascade in models of cocaine use and lays the foundations for further translational work targeting this pathway.
2025-02-26 | GSE270650 | GEO
Project description:Opioids analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It has been recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. Further study indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital acquired bacterial infection. In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital acquired bacterial infection. Citrobacter rodentium is a natural mouse pathogen that models intestinal infection by enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) and causes attaching and effacing lesions and colonic hyperplasia. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) increase in virulence factors expression with C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This is the first study to demonstrate that morphine promotes pathogen dissemination in the context of intestinal C. rodentium infection, indicating morphine modulates virulence factor-mediated adhesion of pathogenic bacteria and induces disruption of mucosal host defense during C. rodentium intestinal infection in mice. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and increased risk of infections, suggesting over-prescription of opioids may increase the risk in the emergence of pathogenic strains and should be used cautiously. Therapeutics directed at maintaining gut homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
2020-02-18 | E-MTAB-7503 | biostudies-arrayexpress
Project description:Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease. Keywords: expression analysis, transgenerational changes due to vinclozolin
2009-01-03 | GSE14269 | GEO