Assessing the effect of interaction between C-reactive protein and gut microbiome on the risks of anxiety and depression.

Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (ß = - 0.009, P = 2.2 × 10-3), G_Akkermansia (ß = - 0.008, P = 7.60 × 10-3), F_Acidaminococcaceae (ß = 0.008, P = 1.22 × 10-2), G_Holdemanella (ß = - 0.007, P = 1.39 × 10-2) and O_Lactobacillales (ß = 0.006, P = 1.79× 10-2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (ß = 0.010, P = 4.00× 10-4), O_Selenomonadales (ß = - 0.010, P = 1.20 × 10-3), O_Clostridiales (ß = 0.009, P = 2.70 × 10-3) and G_Holdemanella (ß = - 0.008, P = 4.20 × 10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.

Probiotics, Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis.

The brain-gut-microbiome axis is a bidirectional communication pathway between the gut microbiota and the central nervous system. The growing interest in the gut microbiota and mechanisms of its interaction with the brain has contributed to the considerable attention given to the potential use of probiotics, prebiotics and postbiotics in the prevention and treatment of depressive disorders. This review discusses the up-to-date findings in preclinical and clinical trials regarding the use of pro-, pre- and postbiotics in depressive disorders. Studies in rodent models of depression show that some of them inhibit inflammation, decrease corticosterone level and change the level of neurometabolites, which consequently lead to mitigation of the symptoms of depression. Moreover, certain clinical studies have indicated improvement in mood as well as changes in biochemical parameters in patients suffering from depressive disorders.

Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial.

Recent animal studies have supported that Lactobacillus plantarum PS128 (PS128) can reduce the severity of anxiety and depression. However, previous studies did not focus on the sleep quality and mood of humans. This study determines whether PS128 reduces the severity of anxiety and depressive symptoms, regulates autonomic nervous system function, and improves sleep quality. Forty participants between 20 and 40 years of age with self-reported insomnia were randomly assigned to two groups, a PS128 group and a placebo group, in a double-blind trial. Participants took two capsules of either PS128 or a placebo after dinner for 30 days. Study measures included subjective depressive symptoms, anxiety and sleep questionnaires, and miniature-polysomnography recordings at baseline and on the 15th and 30th days of taking capsules. Overall, all outcomes were comparable between the two groups at baseline and within the 30-day period, yet some differences were still found. Compared to the control group, the PS128 group showed significant decreases in Beck Depression Inventory-II scores, fatigue levels, brainwave activity, and awakenings during the deep sleep stage. Their improved depressive symptoms were related to changes in brain waves and sleep maintenance. These findings suggest that daily administration of PS128 may lead to a decrease in depressive symptoms, fatigue level, cortical excitation, and an improvement in sleep quality during the deep sleep stage. Daily consumption of PS128 as a dietary supplement may improve the depressive symptoms and sleep quality of insomniacs, although further investigation is warranted.

Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.

BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities. METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions. KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745. CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.

Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: Considerations in a Naturalistic Clinical Setting.

BACKGROUND: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. METHOD: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. RESULTS: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively). CONCLUSION: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

Gut Microbiome Dysbiosis and Depression: a Comprehensive Review.

PURPOSE OF REVIEW: The human gut microbiome is involved in a bi-directional communication pathway with the central nervous system (CNS), termed the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to mediate or modulate various central processes through the vagus nerve. The microbiota-gut-brain axis is involved with the production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. RECENT FINDINGS: Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed in the present investigation include an array of basic science studies that clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to humans. The studies presented in this review demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression.

Fermented foods, the gut and mental health: a mechanistic overview with implications for depression and anxiety.

Mental disorders including depression and anxiety are often comorbid with gut problems, suggesting a bidirectional relationship between mental health and gut function. Several mechanisms might explain this comorbidity, such as inflammation and immune activation; intestinal permeability; perturbations in the hypothalamic-pituitary-adrenal axis; neurotransmitter/neuropeptide dysregulation; dietary deficiencies; and disturbed gut microbiome composition. The potential of modulating the microbiome-gut-brain axis, and subsequently mental health, through the use of functional foods, is an emerging and novel topic of interest. Fermented foods are considered functional foods due to their putative health benefits. The process of microbial fermentation converts food substrates into more nutritionally and functionally rich products, resulting in functional microorganisms (probiotics), substrates that enhance proliferation of beneficial bacteria in the gut (prebiotics), and bioactive components (biogenics). These functional ingredients act biologically in the gastrointestinal tract and have the ability to modify the gut microbiota, influence translocation of endotoxins and subsequent immune activation, and promote host nutrition. This narrative review explores the theoretical potential of the functional components present in fermented foods to alter gut physiology and to impact the biological mechanisms thought to underpin depression and anxiety. Pre-clinical studies indicate the benefits of fermented foods in relieving perturbed gut function and for animal models of depression and anxiety. However, in humans, the literature relating to the relevance of fermented food for treating or preventing depression and anxiety is sparse, heterogeneous and has significant limitations. This review identifies a critical research gap for further evaluation of fermented foods in the management of depression anxiety in humans.

Depression's Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome.

Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Chronic or early-life stress is one of the key risk factors for depression. In addition, a growing body of data implicates chronic inflammation as a major player in depression pathogenesis. More recently, the gut microbiota has emerged as an important regulator of brain and behavior and also has been linked to depression. However, how this holy trinity of risk factors interact to maintain physiological homeostasis in the brain and body is not fully understood. In this review, we integrate the available data from animal and human studies on these three factors in the etiology and progression of depression. We also focus on the processes by which this microbiota-immune-stress matrix may influence centrally mediated events and on possible therapeutic interventions to correct imbalances in this triune.

The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress.

BACKGROUND: Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the "microbiota-gut-brain" axis. METHODS: PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included "pain OR chronic pain" AND "gut microbiota OR metabolites"; "depression OR depressive disorder" AND "gut microbiota OR metabolites". We also searched the reference lists of key articles manually. RESULTS: This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. CONCLUSION: Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.

Fluoxetine ameliorates dysbiosis in a depression model induced by chronic unpredicted mild stress in mice.

Background: Accumulating evidence has shown that neuropsychiatric disorders are associated with gut microbiota through the gut-brain axis. However, the effects of antidepressant treatment on gut microbiota are rarely studied. Here, we investigated whether stress led to gut microbiota changes and whether fluoxetine plays a role in microbiota alteration. Methods: We investigated changes in gut microbiota in a depression model induced by chronic unpredicted mild stress (CUMS) and a restoration model by applying the classic antidepressant drug fluoxetine. Results: We found that stress led to low bacterial diversity, simpler bacterial network, and increased abundance of pathogens, such as Escherichia/Shigella, and conditional pathogens, such as Enterococcus, Vagococcus, and Aerococcus. However, these changes were attenuated by fluoxetine directly and indirectly. Furthermore, the correlation analysis indicated strong correlations between gut microbiota and anxiety- and depression-like behaviors. Conclusions: This study revealed that fluoxetine led to restoration of dysbiosis induced by stress stimulation, which may imply a possible pathway through which one CNS target drug plays its role in reshaping the gut microbiota.

Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes.

Many cross-sectional epidemiological studies have shown the incidence of periodontitis is positive correlated with that of depression. However, their causal relationship and underlying mechanism are largely unknown. Porphyromonas gingivalis (Pg) is the main pathogen for periodontitis. Employing female mice treated with Pg every other day for 4 weeks, we found that Pg-mice showed obvious depression-like behavior, an increased number of activated astrocytes and decreased levels of mature brain derived neurotrophic factor (BDNF) and astrocytic p75NTR in the hippocampus. Both hippocampal injection of BDNF and overexpression of p75NTR in astrocytes alleviated Pg-induced depression-like behavior in mice. Moreover, Pg-lipopolysaccharides (LPS) generated similar phenotypes, which were reversed by the TLR-4 inhibitor TAK242. Our results suggest that Pg-LPS decreases the level of astrocytic p75NTR and then downregulates BDNF maturation, leading to depression-like behavior in mice. Our study provides the first evidence that Pg is a modifiable risk factor for depression and uncovers a novel therapeutic target for the treatment of depression.

From isoniazid to psychobiotics: the gut microbiome as a new antidepressant target.

An awareness of the importance of the gut-brain axis in psychiatric disorders such as depression is increasing. The gut microbiome is a key component of this axis. Gut bacteria can communicate with the brain through a variety of pathways including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan metabolism and the production of various neuroactive compounds. Patients with depression, and other mood and anxiety disorders, show distinct compositional changes in their gut bacteria profile, raising the question about a possible aetiological role for the microbiome in these disorders. Evidence is emerging that the gut microbiome may represent a new potential antidepressant target and the term 'psychobiotic' has been coined to describe bacteria which confer mental health benefits. Gut bacteria are easily accessible and can be altered in a variety of ways including through the use of probiotics, prebiotics and dietary change. Psychobiotics containing various Lactobacillus and Bifidobacterium species have demonstrated the ability to improve mood, reduce anxiety and enhance cognitive function in both healthy populations and patient groups. This article provides an overview of the identification and development of antidepressant psychobiotics, from the preclinical evidence in the laboratory to the more recent encouraging results from human trials.

A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode.

OBJECTIVES: There is evidence that the gut microbiota plays a major role in the pathogenesis of diseases of the central nervous system through the gut-brain axis. The aim of the present study was to analyze gut microbiota composition in bipolar disorder (BD) and its relation to inflammation, serum lipids, oxidative stress, tryptophan (TRP)/kynurenine (KYN) levels, anthropometric measurements and parameters of metabolic syndrome. Further, microbial community differences of individuals with BD compared with healthy controls (HC) were explored. METHODS: In this cross-sectional study, we performed 16S rRNA gene sequencing of stool samples from 32 BD individuals and 10 HC. Laboratory parameters included inflammatory markers, serum lipids, KYN, oxidative stress and anthropometric measures. Microbial community analysis and correlation to clinical parameters was performed with QIIME, differential abundance analysis of taxa encompassed linear discriminant analysis effect size (LEfSe). RESULTS: We found a negative correlation between microbial alpha-diversity and illness duration in BD (R = -0.408, P = 0.021). Furthermore, we identified bacterial clades associated with inflammatory status, serum lipids, TRP, depressive symptoms, oxidative stress, anthropometrics and metabolic syndrome in individuals with BD. LEfSe identified the phylum Actinobacteria (LDA= 4.82, P = 0.007) and the class Coriobacteria (LDA= 4.75, P = 0.010) as significantly more abundant in BD when compared with HC, and Ruminococcaceae (LDA= 4.59, P = 0.018) and Faecalibacterium (LDA= 4.09, P = 0.039) as more abundant in HC when compared with BD. CONCLUSIONS: The present findings suggest that causes and/or consequences of BD may also lie outside the brain. Exploratory research of the gut microbiota in affective disorders like BD may identify previously unknown underlying causes, and offer new research and therapeutic approaches to mood disorders.

Role of Actinobacteria and Coriobacteriia in the antidepressant effects of ketamine in an inflammation model of depression.

Ketamine, an N-methyl-d-aspartic acid receptor (NMDAR) antagonist, elicits rapid-acting and sustained antidepressant effects in treatment-resistant depressed patients. Accumulating evidence suggests that gut microbiota via the gut-brain axis play a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. Here we investigated the role of gut microbiota in the antidepressant effects of ketamine in lipopolysaccharide (LPS)-induced inflammation model of depression. Ketamine (10 mg/kg) significantly attenuated the increased immobility time in forced swimming test (FST), which was associated with the improvements in α-diversity, consisting of Shannon, Simpson and Chao 1 indices. In addition to α-diversity, ß-diversity, such as principal coordinates analysis (PCoA), and linear discriminant analysis (LDA) coupled with effect size measurements (LEfSe), showed a differential profile after ketamine treatment. Furthermore, a total of 30 bacteria were significantly altered in the LPS + saline treated mice and LPS + ketamine treated mice. Interestingly, two bacteria, including the phylum Actinobacteria and the class Coriobacteriia were significantly correlated with the immobility time of FST. Importantly, the receiver operating characteristic (ROC) curves demonstrated that the phylum Actinobacteria and the class Coriobacteriia were potential biomarker for the antidepressant effects of ketamine in an inflammation model. These findings suggest that antidepressant effects of ketamine might be related to the regulation of abnormal composition of gut microbiota, and that the phylum Actinobacteria and the class Coriobacteriia might be potential biomarkers for ketamine's antidepressant efficacy.

Psychobiome Feeding Mind: Polyphenolics in Depression and Anxiety.

Recently gut bacterial populations seem to be involved in many functions and in the pathogenesis of several medical conditions. Traditionally the intestinal microbiome has been recognized to play an important role in metabolizing food compounds in simpler chemical structures for the absorption of different nutrients, and in maintenance control of gastrointestinal pathogens species. Bacterial populations are implicated in a complicated network of interactions within the immune system, epithelial cells local endocrine system, that affects the peripheral and the central nervous system, via blood circulation. Microbiome influencing the mind via immune, endocrine and metabolic signalling, is able to exert some clinical effects in different mental diseases. It releases endocrine substances through several pathways involved in the modulation of neuroinflammation and production of several neurotrasmitter precursors. It has recently been named psychobiome. It is known that phenolic compounds are able to influence microbiome proliferation and to exert several roles, especially regarding neuroinflammation in depressive and anxious behaviour. The clinical effects are reported in the literature. The aim of this study is to highlight the interaction between polyphenols and microbiota- gut-brain axis.

Possible role of the gut microbiota-brain axis in the antidepressant effects of (R)-ketamine in a social defeat stress model.

Accumulating evidence suggests that the gut microbiota-brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. (R)-ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine enantiomers. The role of the gut microbiota in the antidepressant effects of ketamine enantiomers in a chronic social defeat stress (CSDS) model of depression was examined using 16S ribosomal RNA gene sequencing of fecal samples. At the phylum level, CSDS-susceptible mice showed alterations in the levels of Tenericutes and Actinobacteria; however, neither ketamine enantiomers influenced these alterations. At the class level, both ketamine enantiomers significantly attenuated the increase in the levels of Deltaproteobacteria in the susceptible mice after CSDS. Furthermore, (R)-ketamine, but not (S)-ketamine, significantly attenuated the reduction in the levels of Mollicutes in the susceptible mice. At the genus level, both ketamine enantiomers significantly attenuated the decrease in the levels of Butyricimonas in the susceptible mice. Notably, (R)-ketamine was more potent than (S)-ketamine at reducing the levels of Butyricimonas in the susceptible mice. In conclusion, this study suggests that the antidepressant effects of two enantiomers of ketamine in CSDS model may be partly mediated by the restoration of the gut microbiota. Furthermore, the specific effect of (R)-ketamine on the levels of Mollicutes and Butyricimonas may explain its robust antidepressant action.

[Gut microbiota and depressive symptoms].

The gut microbiota is believed to affect a wide variety of mental disorders, including depression. The hypothesis involves bacterial signalling to the host through metabolic, endocrinal, immunologic and neuronal pathways. Few studies of patients with depression have shown altered microbiota profiles and increased levels of systemic endotoxin, which can be detected by leucocytes and result in expression of cytokines. Studies performed so far have lacked statistical power and provide no causal explanation for the gut-brain hypothesis. Further research into the matter is certainly warranted.

Feeding Systems and the Gut Microbiome: Gut-Brain Interactions With Relevance to Psychiatric Conditions.

BACKGROUND: Physical and mental health is dependent on the environment, and feeding is a prime example of this environmental exchange. While the hypothalamus controls both feeding behavior and the stress response, the integration of the neural control centers and the peripheral gut allows for disruption in the gastrointestinal systems and dysfunctional communication to the brain. OBJECTIVE: The purpose of this review is to familiarize clinicians with the physiology controlling feeding behavior and its implications for psychiatric conditions, such as anorexia nervosa and depression. Growing understanding of how integrated bacterial life is in the body has shown that gut bacteria regulate basic physiologic processes and are implicated in various disease states and contribute to regulation of mood. Responses to stress have effects on feeding behavior and mood and the regulation of the stress response by the gut microbiota could contribute to the dysfunction seen in patients with psychiatric illnesses. CONCLUSIONS: Gut microbiota may contribute to dysfunction in psychiatric illnesses. New opportunities to modulate existing gut microbiota using probiotics could be novel targets for clinical interventions.

Depressed gut? The microbiota-diet-inflammation trialogue in depression.

PURPOSE OF REVIEW: According to the WHO reports, around 350 million people worldwide suffer from depression. Despite its high prevalence, the complex interaction of multiple mechanisms underlying depression still needs to be elucidated. RECENT FINDINGS: Over the course of the last few years, several neurobiological alterations have been linked to the development and maintenance of depression. One basic process that seems to link many of these findings is inflammation. Chronic inflammation has been associated with both biological factors such as excessive neurotransmitter concentrations as well as psychological processes such as adult stress reactivity and a history of childhood trauma. As a balanced microbial community, modulated by diet, is a key regulator of the host physiology, it seems likely that gut microbiota plays a role in depression. SUMMARY: The review summarizes the existent literature on this emerging research field and provides a comprehensive overview of the multifaceted links between the microbiota, diet, and depression. Several pathways linking early life trauma, pharmacological treatment effects, and nutrition to the microbiome in depression are described aiming to foster the psychotherapeutic treatment of depressed patients by interventions targeting the microbiota.

Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice.

Accumulating evidence suggests that abnormalities in the composition of the gut microbiota may play a role in the pathogenesis of depression. Although approximately 30% mice are resilient to chronic social defeat stress (CSDS), the role of gut microbiota in this stress resilience is unknown. In this study, male C57BL/6 mice were exposed to a different CD1 aggressor mouse for 10 min on 10 consecutive days. A social interaction test was applied to distinguish between resilient and susceptible mice. Using 16S rRNA analysis, we examined the composition of gut microbiota in feces from control, resilient, and susceptible mice. The marked appearance of Bifidobacterium was detected in the resilient mice, whereas in the control and susceptible mice, Bifidobacterium were below the detection limit. Oral intake of Bifidobacterium significantly increased the number of resilient mice after CSDS compared with vehicle-treated mice. These findings suggest that Bifidobacterium may confer resilience to CSDS. Therefore, supplementation of Bifidobacterium may prevent the onset of depression from stress in humans. In addition, supplementation of Bifidobacterium may prevent or minimize relapse from remission induced by inflammation and/or stress in depressed patients.