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Objectives: Recurrent aphthous ulcer (RAU) is a prevalent oral mucosal disease, affecting around 20% of the global population. It can greatly impair the quality of life for affected individuals. However, the exact etiology of RAU remains unknown. Subjects and Methods: 16S rRNA sequencing (16S rRNA‐seq) and non‐targeted liquid chromatography‐mass spectrometry (LC–MS) were employed to investigate the salivary microbiota and metabolic phenotype between RAU patients (N = 61) and healthy controls (HCs) (N = 105). Results: Findings from 16S rRNA ‐seq indicated reduced oral microbial diversity in RAU patients compared to HCs, but increased interactions. Clinical variables did not show any significant association with the overall diversity of oral microbiota in RAU patients. However, significant correlations were observed between specific microorganisms and clinical variables. LC–MS results revealed dysregulation of amino acid, lipid, nucleotide, and caffeine metabolism in RAU patients. Furthermore, correlation analysis of 16S rRNA‐seq and LC–MS data revealed a significant association between salivary microbiota and metabolites in RAU patients. Conclusions: Our study revealed notable differences in salivary microbiota and metabolic profiles between RAU patients and HCs, indicating a strong link between oral microbiota dysbiosis, metabolic disturbances, and the onset and progression of RAU. [ABSTRACT FROM AUTHOR]

Post-stroke depression (PSD) is the most common and severe neuropsychiatric complication after stroke. However, the molecular mechanism of PSD is still unclear. Previous studies have identified peripheral blood and urine metabolites associated with PSD using metabolomics techniques. We searched and systematically summarized metabolites that may be involved in metabolic changes in peripheral blood and urine of patients with PSD from the Metabolite Network of Depression Database (MENDA) and other biomedical databases. MetaboAnalyst5.0 software was used for pathway analysis and enrichment analysis of differential metabolites, and subgroup analyses were performed according to tissue types and metabolomics techniques. We identified 47 metabolites that were differentially expressed between patients with and without PSD. Five differential metabolites were found in both plasma and urine, including L-glutamic acid, pyroglutamic acid, palmitic acid, L-phenylalanine, and L-tyrosine. We integrated these metabolites into metabolic pathways, and six pathways were significantly altered. These pathways could be roughly divided into three modules including amino acid metabolism, nucleotide metabolism, and glucose metabolism. Among them, the most significantly altered pathway was "phenylalanine metabolism" and the pathway containing the most associated metabolites was "aminoacyl-tRNA biosynthesis", which deserve further study to elucidate their role in the molecular mechanism of PSD. In summary, metabolic changes in peripheral blood and urine are associated with PSD, especially the disruption of "phenylalanine metabolism" and "aminoacyl-tRNA biosynthesis" pathways. This study provides clues to the metabolic characteristics of patients with PSD, which may help to elucidate the molecular pathogenesis of PSD. [ABSTRACT FROM AUTHOR]

Background: Our understanding of the molecular mechanisms of depression remains largely unclear. Previous studies have shown that the prefrontal cortex (PFC) is among most important brain regions that exhibits metabolic changes in depression. A comprehensive analysis based on candidate metabolites in the PFC of animal models of depression will provide valuable information for understanding the pathogenic mechanism underlying depression. Methods: Candidate metabolites that are potentially involved in the metabolic changes of the PFC in animal models of depression were retrieved from the Metabolite Network of Depression Database. The significantly altered metabolic pathways were revealed by canonical pathway analysis, and the relationships among altered pathways were explored by pathway crosstalk analysis. Additionally, drug-associated pathways were investigated using drug-associated metabolite set enrichment analysis. The interrelationships among metabolites, proteins, and other molecules were analyzed by molecular network analysis. Results: Among 88 candidate metabolites, 87 altered canonical pathways were identified, and the top five ranked pathways were tRNA charging, the endocannabinoid neuronal synapse pathway, (S)-reticuline biosynthesis II, catecholamine biosynthesis, and GABA receptor signaling. Pathway crosstalk analysis revealed that these altered pathways were grouped into three interlinked modules involved in amino acid metabolism, nervous system signaling/neurotransmitters, and nucleotide metabolism. In the drug-associated metabolite set enrichment analysis, the main enriched drug pathways were opioid-related and antibiotic-related action pathways. Furthermore, the most significantly altered molecular network was involved in amino acid metabolism, molecular transport, and small molecule biochemistry. Conclusions: This study provides important clues for the metabolic characteristics of the PFC in depression. [ABSTRACT FROM AUTHOR]

Introduction: Recently, an increasing number of studies have focused on commensal microbiota. These microorganisms have been suggested to impact human health and disease. However, only a small amount of data exists to support the assessment of the influences that commensal microbiota exert on olfactory function. Methods: We used a buried food pellet test (BFPT) to investigate and compare olfactory functions in adult, male, germ-free (GF) and specific-pathogen-free (SPF) mice, then examined and compared the metabolomic profiles for olfactory bulbs (OBs) isolated from GF and SPF mice to uncover the mechanisms associated with olfactory dysfunction. Results: We found that the absence of commensal microbiota was able to influence olfactory function and the metabolic signatures of OBs, with 38 metabolites presenting significant differences between the two groups. These metabolites were primarily associated with disturbances in glycolysis, the tricarboxylic acid (TCA) cycle, amino acid metabolism, and purine catabolism. Finally, the commensal microbiota regulation of metabolic networks during olfactory dysfunction was identified, based on an integrated analysis of metabolite, protein, and mRNA levels. Conclusion: This study demonstrated that the absence of commensal microbiota may impair olfactory function and disrupt metabolic networks. These findings provide a new entry-point for understanding olfactory-associated disorders and their potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a prevalent and serious mental disorder with high rates of suicide and disability. However, the underlying pathogenesis of MDD is complicated and remains largely unclear. An integrated analysis of multiple types of omics data may improve comprehensive understanding of the entire molecular mechanism of MDD. In this study, we applied an integrated analysis of gas chromatography/mass spectrometry (GC–MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics to investigate changes in the hippocampus in the chronic unpredictable mild stress (CUMS) rat model of depression. Only the stress-susceptible rats in the CUMS group were selected for profiling against controls. Differential analysis identified 30 metabolites and 170 proteins between the two groups. The integrated analyses revealed four major changes in the hippocampus of CUMS rats: (1) impairment in amino acid metabolism and protein synthesis/degradation; (2) dysregulation of glutamate and glycine metabolism and their transport/catabolism related proteins; (3) disturbances in fatty acid and glycerophospholipid metabolism accompanied by alterations in the corresponding metabolic enzymes; (4) abnormal expression of synapse-associated proteins. These results provide further important insights into the pathophysiology of depression and may help identify potential targets for antidepressant drugs. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography–mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. “Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry” was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats. [ABSTRACT FROM AUTHOR]