RESUMO
BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
Assuntos
Anorexia , Proteína C-Reativa , Transtorno Depressivo Maior , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/microbiologia , Feminino , Adulto , Masculino , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Anorexia/microbiologia , Anorexia/sangue , Inflamação/sangue , Pessoa de Meia-Idade , Estudos de Casos e Controles , RNA Ribossômico 16S/genética , Adulto JovemRESUMO
Purpose: The diversity and composition of the oral and gut microbiota of depressed rats were analyzed to explore the microbiological etiology of major depressive disorder (MDD). Methods: The depressed rat model was established by inducing chronic unpredictable mild stress (CUMS). After the establishment of the model, body weight measurements and behavioral tests were conducted. The diversity and composition of oral and gut microbiota were analyzed using 16SrRNA sequencing. Results: There were significant differences in the alpha and beta diversity of the oral microbiota of rats in the CUMS and control groups. The top three most abundant genera in the oral microbiota were Rothia, Psychrobacter, and Streptococcus. Linear discriminant analysis effect size (LEfSe) analysis showed that the abundance of Rothia decreased and that of Psychrotrophs increased in the CUMS group, and the differences were statistically significant. The top three most abundant genera in the gut microbiota were Lactobacillus, Ruminococcus and Oscillospira. LEfSe analysis showed that the abundance of Ruminococcus decreased in the CUMS group, and the difference was statistically significant. Spearman correlation analysis was performed to analyze the differential microbiota and depression-like behavior, which showed that differential microbiota significantly correlated with body weight, total distance traveled, average speed, and number of rearing. Spearman correlation analysis of oral and gut differential microbiota demonstrated a strong positive correlation between Facklamia in the oral cavity and Enterococcus, Streptococcus in the intestine (r=0.64-0.73, P<0.01); along with a strong negative correlation between Desulfovibrio in the oral cavity and Enterococcus, Turicibacter in the intestine(r=-0.51--0.72, P<0.05). Conclusion: Significant differences were observed in the diversity and composition of oral and gut microbiota between the CUMS depression model and control groups. Modulating the oral and gut microbiota may have positive effects on MDD.
RESUMO
OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.
Assuntos
Proteína C-Reativa , Transtorno Depressivo Maior , Fezes , Microbioma Gastrointestinal , Humanos , Transtorno Depressivo Maior/microbiologia , Transtorno Depressivo Maior/sangue , Feminino , Masculino , Adulto , Proteína C-Reativa/análise , Fezes/microbiologia , Pessoa de Meia-Idade , Sintomas Inexplicáveis , RNA Ribossômico 16S/genética , Estudos de Casos e Controles , Adulto JovemRESUMO
Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.
Assuntos
Microbioma Gastrointestinal , Animais , Humanos , Camundongos , Depressão/terapia , Ácidos Graxos Voláteis/metabolismo , Transplante de Microbiota Fecal , FezesRESUMO
The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.