Gut microbiome and major depressive disorder: insights from two-sample Mendelian randomization.

BACKGROUND: Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut. METHODS: We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately. RESULTS: Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43). CONCLUSIONS: Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

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.

The Microbiome in Child and Adolescent Psychiatry.

Recent research has increasingly emphasized the function of the microbiome in human health. The gut microbiome is essential for digesting food and seems to play a vital role in mental health as well. This review briefly overviews the gut microbiome and its interplay with the central nervous system. We then summarize some of the latest findings on the possible role of the microbiome in psychiatric disorders in children and adolescents. In particular, we focus on autism spectrum disorder, attention-deficit/hyperactivity disorder, anorexia nervosa, bipolar disorder, and major depressive disorder. Although the role of microbiota in mental development and health still needs to be researched intensively, it has become increasingly apparent that the impact of microbiota must be considered to better understand psychiatric disorders.

Updated review of research on the gut microbiota and their relation to depression in animals and human beings.

The gut microbiota are being called the human "second brain," as they play a key role in the regulation of the central nervous system (CNS). Recent findings provide strong evidence for the presence of bidirectional communication networks between the gut microbiota and the CNS, and such crosstalk has been correlated with alterations in major depressive disorder (MDD) and other psychiatric disorders. Further, germ-free animal models have been used to investigate the effect of the microbiota on MDD and other psychiatric disorders, which have greatly expanded our knowledge of the role of the microbiota in the etiology of MDD and promoted causality studies of this psychiatric disorder and others as well. In this review, we first introduce the methodological approaches used for microbiota research and then provide an overview of current research progress on the modulatory function and composition of the gut microbiota in MDD and the therapeutic effect of probiotics that has been gained using data from human studies as well as animal experiments. Future research should focus on identification and characterization of specific bacterial strains involved in MDD with the hope of applying these findings in the prevention and treatment of MDD.

Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case-control study.

Background: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment. Methods: In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry. Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment. Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results. Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

Depression: A Gut "Microbiome" Feeling!

ABSTRACT: Burgeoning body of evidence from neuroscience is pouring in highlighting a potential association between gut microbiota with the pathophysiology of depression and anxiety. Manipulation of gut microbiota may be then useful to decode this role and to provide novel therapeutics for major depressive disorder (MDD), developing microbiota-related biomarkers to stratify patients at risk and to delineate more homogeneous biotypes of MDD.

Effect of probiotic and prebiotic versus placebo on appetite in patients with major depressive disorder: post hoc analysis of a randomised clinical trial.

BACKGROUND: Poor appetite and weight loss are common in melancholic depression. Probiotics and prebiotics have the capacity to affect host behaviour, appetite and weight change by modulating the gut microbiome. The aim of this post hoc analysis was to investigate the effect of supplementation with probiotic and prebiotic on appetite, in parallel with body mass index (BMI), weight and energy intake, in patients with major depressive disorder (MDD). METHODS: We extracted data from a clinical trial with 81 patients. The participants were randomly assigned to receive probiotic (Lactobacillus helveticus and Bifidobacterium longum), prebiotic (galactooligosaccharide) or placebo for 8 weeks. Appetite, weight, BMI, dietary intake, serum leptin and physical activity were measured. Subjective appetite rating was evaluated every 2 weeks using visual analogue scales (VAS) to assess satiety, hunger, fullness and desire to eat. Serum leptin was measured by an enzyme-linked immunosorbent assay. Physical activity was measured using the international physical activity questionnaire. A repeated measures analysis of variance model was used to analyse VAS data and analysis of variance/analysis of covariance models for dietary intake, BMI, weight and leptin data. RESULTS: VAS data analyses indicated no significant intervention-time interactions but did show a significant increase over time for desire to eat within the probiotic group (P = 0.025). No significant difference in either BMI or weight was seen among the groups. Energy intake and leptin were significantly increased in the probiotic group compared to the prebiotic. CONCLUSIONS: Overall, probiotic supplementation for 8 weeks among MDD patients resulted in improvement of appetite, whereas prebiotic administration had no significant effect on appetite.

A review of the antimicrobial side of antidepressants and its putative implications on the gut microbiome.

OBJECTIVE: Serotonin reuptake inhibitors are the predominant treatment for major depressive disorder. In recent years, the diversity of the gut microbiota has emerged to play a significant role in the occurrence of major depressive disorder and other mood and anxiety disorders. Importantly, the role of the gut microbiota in the treatment of such disorders remains to be elucidated. Here, we provide a review of the literature regarding the effects of physiologically relevant concentrations of serotonin reuptake inhibitors on the gut microbiota and the implications this might have on their efficacy in the treatment of mood disorders. METHODS: First, an estimation of gut serotonin reuptake inhibitor concentrations was computed based on pharmacokinetic and gastrointestinal transit properties of serotonin reuptake inhibitors. Literature regarding the in vivo and in vitro antimicrobial properties of serotonin reuptake inhibitors was gathered, and the estimated gut concentrations were examined in the context of these data. Computer-based investigation revealed putative mechanisms for the antimicrobial effects of serotonin reuptake inhibitors. RESULTS: In vivo evidence using animal models shows an antimicrobial effect of serotonin reuptake inhibitors on the gut microbiota. Examination of the estimated physiological concentrations of serotonin reuptake inhibitors in the gastrointestinal tract collected from in vitro studies suggests that the microbial community of both the small intestine and the colon are exposed to serotonin reuptake inhibitors for at least 4 hours per day at concentrations that are likely to exert an antimicrobial effect. The potential mechanisms of the effect of serotonin reuptake inhibitors on the gut microbiota were postulated to include inhibition of efflux pumps and/or amino acid transporters. CONCLUSION: This review raises important issues regarding the role that gut microbiota play in the treatment of mood-related behaviours, which holds substantial potential clinical outcomes for patients suffering from major depressive disorder and other mood-related disorders.

Moody microbiome: Challenges and chances.

Growing evidence link gut microbiome to the development and maturation of the central nervous system, which are regulated by microbiota potentially through stress response, neurotransmitter, neuroimmune, and endocrine pathways. The dysfunction of such microbiota-gut-brain axis is implicated in neuropsychiatric disorders, depression, and other stress-related conditions. Using affective disorders as our primary outcomes, we inspect the current evidence of microbiota studies mainly in human clinical samples. Additionally, to restore microbiome equilibrium in bacteria diversity and abundance might represent a novel strategy to prevent or treat mood symptoms. We reviewed findings from clinical trials regarding efficacy of probiotics supplement with or without antidepressant treatment, and adjuvant antimicrobiotics treatment. In microbiota studies, the considerations of host-microbiota interaction and bacteria-bacteria interaction are discussed. In conclusion, the roles of microbiota in depression and mania state are not fully elucidated. One of the challenges is to find reliable targets for functional analyses and experiments. Notwithstanding some inconsistencies and methodological limitations across studies, results from recent clinical trials support for the beneficial effects of probiotics on alleviating depressive symptoms and increasing well-beings. Moreover, modifying the composition of gut microbiota via antibiotics can be a viable adjuvant treatment option for individuals with depressive symptoms.

Differences in the association between persistent pathogens and mood disorders among young- to middle-aged women and men in the U.S.

BACKGROUND: A growing literature supports the role of immune system alterations in the etiology of mood regulation, yet there is little population-based evidence regarding the association between persistent pathogens, inflammation and mood disorders among younger women and men in the U.S. METHODS: We used data from the National Health and Nutrition Examination Survey III on individuals 15-39 years of age assessed for major depression, dysthymia, and/or bipolar disorder I and tested for cytomegalovirus (N=6825), herpes simplex virus (HSV)-1 (N=5618) and/or Helicobacter pylori (H. pylori) (N=3167) seropositivity as well as C-reactive protein (CRP) level (N=6788). CMV immunoglobulin G (IgG) antibody level was also available for a subset of women (N=3358). We utilized logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between pathogens, CRP levels and each mood disorder overall and among women and men, separately. RESULTS: H. pylori seropositivity was associated with increased odds of dysthymia (OR 2.37, 95% confidence interval (CI): 1.07, 5.24) among women, but decreased odds among men (OR 0.51, 95% CI: 0.28, 0.92). CMV seropositivity was also associated with lower odds of depression (OR 0.54, 95% CI: 0.32, 0.91) among men, while elevated CMV IgG level was marginally associated with increased odds of mood disorders among women. Associations were not mediated by CRP level. CONCLUSIONS: Our findings suggest that persistent pathogens such as CMV and H. pylori may differentially influence mood disorders among women and men, warranting further investigation into biological and/or sociocultural explanations for the contrasting associations observed.

Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.

Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities.

BACKGROUND: Persistent low-grade immune-inflammatory processes, oxidative and nitrosative stress (O&NS), and hypothalamic-pituitary-adrenal axis activation are integral to the pathophysiology of major depressive disorder (MDD). The microbiome, intestinal compositional changes, and resultant bacterial translocation add a new element to the bidirectional interactions of the gut-brain axis; new evidence implicates these pathways in the patho-aetiology of MDD. In addition, abnormalities in the gut-brain axis are associated with several chronic non-communicable disorders, which frequently co-occur in individuals with MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM). METHODS: We searched the PubMed/MEDLINE database up until May 1, 2016 for studies which investigated intestinal dysbiosis and bacterial translocation (the 'leaky gut') in the pathophysiology of MDD and co-occurring somatic comorbidities with an emphasis on IBS, CFS, obesity, and T2DM. RESULTS: The composition of the gut microbiota is influenced by several genetic and environmental factors (e.g. diet). Several lines of evidence indicate that gut-microbiota-diet interactions play a significant pathophysiological role in MDD and related medical comorbidities. Gut dysbiosis and the leaky gut may influence several pathways implicated in the biology of MDD, including but not limited to immune activation, O&NS, and neuroplasticity cascades. However, methodological inconsistencies and limitations limit comparisons across studies. CONCLUSIONS: Intestinal dysbiosis and the leaky gut may constitute a key pathophysiological link between MDD and its medical comorbidities. This emerging literature opens relevant preventative and therapeutic perspectives.

[Gut microbiome and major depressive disorder : The other side of ourselves]. / Dickdarmmikrobiom und Depression : Die andere Seite unseres Selbst.

Microbiological ecology and its ambition to describe the complete genome of complex living communities as a whole, have given us powerful tools to characterize the human gut microbiome on a genetic and, hence, taxonomic and abundance level; for a decade now, they have become sufficiently inexpensive, fast and feasible. Thus, opportunities arose to have a fresh and closer look at the microbiota-gut-brain-axis and its impact on human health; this axis comprises a complex multisystemic network of multidirectional interactions between brain and gut including influences beyond one generation. Gnotobiotic animal models have become essential for specific research targets. Combining gut microbiome analysis with observations on the hypothalamus-pituitary-adrenal axis and various aspects of inflammation helped to gain first insights into the role of the microbiota-gut-brain-axis in depressive disorders. Therapeutic endeavors with psychobiotics have not yet shown their value in clinical studies.

The impact of gut microbiota on brain and behaviour: implications for psychiatry.

PURPOSE OF REVIEW: The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. RECENT FINDINGS: Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. SUMMARY: The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.

Altered fecal microbiota composition in patients with major depressive disorder.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Gut Microbiome Patterns Associated With Treatment Response in Patients With Major Depressive Disorder.

OBJECTIVES: Compelling animal data exists examining the impact of the gut microbiome on the brain, but work is required to translate these findings in a clinical population. We sought to do this by exploring the effects of antidepressant medications on the gut microbiota, and establishing a baseline Major Depressive Disorder (MDD) gut phenotype. METHODS: Participants with a primary diagnosis of MDD (n = 15) who were nonmedicated were recruited and followed over 6 months. Stool samples were collected prior to treatment initiation and 3 and 6 months following treatment. 16S rRNA sequencing was employed in order to analyze the gut microbial community profile. Symptom severity was measured by the Beck Depression Inventory. Alpha diversity metrics revealed no significant difference in the community diversity across any of the time-points. RESULTS: Comparison of within-group versus between-group distances revealed a lack of clustering of samples based on time-point, suggesting no significant change in the microbiota across treatment duration. When analyzed based on treatment response, however, patients in the responder group exhibited greater phylogenetic diversity than non-responders (Mann-Whitney U = 5, p = 0.026). At 3-months, 35 Operational Taxonomic Units (OTUs) were significantly different between groups and at 6-months, 42 OTUs were significantly different between responders and non-responders. CONCLUSIONS: These observations indicate that antidepressant medications alter the gut microbiota of patients with MDD, with disparate effects in responders versus non responders. This supports the concept of a microbiota phenotype associate with treatment response in MDD.

The gastrointestinal tract microbiome, probiotics, and mood.

Mental health is closely linked to physical health. Depression (e.g., major depression) is highly prevalent worldwide and a major cause of disability. In a subgroup with treatment-resistant depression, standard pharmacotherapy interventions provide small if any incremental improvement in patient outcomes and may also require the application of an alternate approach. Therefore, in addition to the standard pharmacotherapies prescribed, patients will also be advised on the benefits of psychological counseling, electroconvulsive therapy, and transcranial magnetic stimulation or increasing physical activity and reducing harmful substance consumption. Numerous nutraceuticals have a beneficial role in treatment-resistant depression and include, herbal medicines of which Hypericum perforatum is the best studied, omega-3 fatty acid preparations, S-Adenosyl-L-Methionine (SAMe), various mineral formulations (e.g., magnesium) and folate (singly or in combination with B group vitamins) are prescribed to a lesser extent. Furthermore, a largely neglected area of research activity has been the role of live probiotic cultures that contribute to repairing dysbiosis (a leaky gut barrier abnormality) in the gastrointestinal tract (GIT). In this commentary, we build a hypothesis that in addition suggests that GIT metabolites that are elaborated by the microbiome cohort may provide novel and significant avenues for efficacious therapeutic interventions for mood disorders. We posit that the microbiome in the gastrointestinal tract is implicit as an important participant for the amelioration of adverse mood conditions via the diverse metabolic activities provided by live beneficial bacteria (probiotics) as an active adjuvant treatment. This activity is in part triggered by a controlled release of reactive oxygen species (ROS) and hence further questions the antioxidant/oxidative stress postulate.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

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.

Research Progress on Mechanisms of Modulating Gut Microbiota to Improve Symptoms of Major Depressive Disorder.

Major depressive disorder (MDD) is a clinical condition that significantly impacts patients' physical and mental well-being, quality of life, and social functioning. The pathogenesis of MDD remains unclear, but accumulating evidence suggests a close relationship between gut microbiota and the occurrence and progression of MDD. Gut microbiota refers to the microbial community in the human intestine, which engages in bidirectional communication with the host via the "gut-brain axis" and plays a pivotal role in influencing the host's metabolism, immune system, endocrine system, and nervous system. Modulating gut microbiota entails restoring the balance and function of the intestinal flora through methods such as probiotic intake, fecal transplantation, and dietary intervention. Such modulation has been shown to effectively alleviate depressive symptoms in the host. This review synthesizes recent advancements in research on gut microbiota modulation for ameliorating depressive symptoms and can serve as a foundation for further exploration of the gut microbiota's role in MDD and its potential therapeutic benefits.

Impacts of microbiota and its metabolites through gut-brain axis on pathophysiology of major depressive disorder.

Major depressive disorder (MDD) is characterized by a high rate of recurrence and disability, which seriously affects the quality of life of patients. That's why a deeper understanding of the mechanisms of MDD pathology is an urgent task, and some studies have found that intestinal symptoms accompany people with MDD. The microbiota-gut-brain axis is the bidirectional communication between the gut microbiota and the central nervous system, which was found to have a strong association with the pathogenesis of MDD. Previous studies have focused more on the communication between the gut and the brain through neuroendocrine, neuroimmune and autonomic pathways, and the role of gut microbes and their metabolites in depression is unclear. Metabolites of intestinal microorganisms (e.g., tryptophan, kynurenic acid, indole, and lipopolysaccharide) can participate in the pathogenesis of MDD through immune and inflammatory pathways or by altering the permeability of the gut and blood-brain barrier. In addition, intestinal microbes can communicate with intestinal neurons and glial cells to affect the integrity and function of intestinal nerves. However, the specific role of gut microbes and their metabolites in the pathogenesis of MDD is not well understood. Hence, the present review summarizes how gut microbes and their metabolites are directly or indirectly involved in the pathogenesis of MDD.