Project description:Major depressive disorder is caused by gene-environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the mechanisms by which the gut microbiota modulates depression remain elusive. Herein, we detected the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs) and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level. We also performed functional analysis to explore the microbial-regulated pathological mechanisms of depression. Two hundred mRNAs, 358 lncRNAs and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differentially expressed mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting the differentially expressed mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, we constructed a microbial-regulated lncRNA-miRNA-mRNA network based on RNA-RNA interactions. According to the competitive endogenous RNA hypothesis, two neurodevelopmental ceRNA sub-networks implicating in depression were identified. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.
2021-12-31 | GSE189159 | GEO
Project description:Gut microbiota in patients with major depressive disorder
Project description:This study investigated whether dietary poricoic acid A (PAA) alleviates chronic unpredictable stress (CUS)-induced depressive-like behaviors in mice by modulating the gut microbiota-immune axis. Male C57BL/6J mice were subjected to CUS and treated with PAA. Results showed that PAA alleviated depressive- and anxiety-like behaviors, reduced hippocampal neuronal damage, and restored gut microbiota composition by suppressing harmful bacteria like Ligilactobacillus murinus while promoting beneficial taxa such as Akkermansia muciniphila and Lactobacillus reuteri. Hippocampal transcriptomics revealed that PAA modulated immune cell infiltration by reducing M1 and restoring M2 macrophages, with significant correlations between gut microbial taxa and hippocampal immune gene expression. Functional analyses indicated that PAA regulated pathways related to synaptic plasticity and neuroinflammation, which was confirmed by qPCR and Western blot showing restored expression of HSP90B1, RPS6KB2, IGF2BP2, and COL4A5. In conclusion, dietary PAA alleviates depressive-like behaviors in CUS mice by remodeling the gut microbiota and modulating the hippocampal M1/M2 macrophage balance via the gut-brain axis, supporting its potential as a prebiotic-like nutritional agent for major depressive disorder.
Project description:Major depressive disorder is caused by gene-environment interactions and the gut microbiota plays a pivotal role in the development of depression. However, the mechanisms by which the gut microbiota modulates depression remain elusive. Herein, we detected the differentially expressed hippocampal long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs) and microRNAs (miRNAs) between mice inoculated with gut microbiota from major depressive disorder patients or healthy controls, to identify the effects of gut microbiota-dysbiosis on gene regulation patterns at the transcriptome level. We also performed functional analysis to explore the microbial-regulated pathological mechanisms of depression. Two hundred mRNAs, 358 lncRNAs and 4 miRNAs were differentially expressed between the two groups. Functional analysis of these differentially expressed mRNAs indicated dysregulated inflammatory response to be the primary pathological change. Intersecting the differentially expressed mRNAs with targets of differentially expressed miRNAs identified 47 intersected mRNAs, which were mainly related to neurodevelopment. Additionally, we constructed a microbial-regulated lncRNA-miRNA-mRNA network based on RNA-RNA interactions. According to the competitive endogenous RNA hypothesis, two neurodevelopmental ceRNA sub-networks implicating in depression were identified. This study provides new understanding of the pathogenesis of depression induced by gut microbiota-dysbiosis and may act as a theoretical basis for the development of gut microbiota-based antidepressants.
Project description:Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Epigenetic study of MZ twins discordant for Major Depressive Disorder
Project description:Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, associated with gut microbiota dysbiosis. While global studies have explored this link, region-specific microbial profiles remain underreported. This pilot study aimed to characterize and compare, for the first time, the gut microbiota of Lebanese UC patients and healthy controls using 16S rRNA gene sequencing (V3–V4 region). Fecal samples from 11 UC patients and 11 healthy individuals were analyzed. Alpha and beta diversity metrics were computed, and gut microbial composition was assessed across taxonomic levels. Statistical comparisons used Mann-Whitney and Fisher’s exact tests. UC patients showed significantly reduced microbial diversity based on Faith’s Phylogenetic Diversity and Shannon index (p < 0.05), though evenness was unaffected. Beta diversity also revealed significant group-level dissimilarities (p < 0.05). At the phylum level, Bacteroidota was elevated in UC, while Bacillota and Actinomycetota were reduced. Genera such as Ruminococcus, Fusicatenibacter, Mediterraneibacter, Eubacterium, and Coprococcus were depleted in UC. Faecalibacterium, commonly reduced in UC, showed no significant difference. This first analysis of gut microbiota in Lebanese UC patients reveals a distinct microbial signature that partially diverges from global trends, supporting the need for region-specific microbiome studies and personalized microbiota-targeted therapies.
Project description:Genome-wide MeDIP-Sequencing of 23 monozygotic twin pairs (n=46) from Australia discordant for major depressive disorder (MDD). MeDIP-seq of 23 monozygotic twin pairs discordant for major depressive disorder. MZ twin pairs were compared to identify significantly differently methylated sites associated with MDD.