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"Gut-brain axis": Review of the role of the probiotics in anxiety and depressive disorders.
BACKGROUND: Depressive disorders are the leading cause of disability worldwide and together with anxiety contribute to a very high burden of disease. Therefore, improving their treatment is a significant medical research target: The role of probiotics is a topic of great interest for the current research in this field. OBJECTIVES: To explore the current literature about the impact of probiotics on anxious and depressive symptoms. METHODS: Scoping review following the PRISMA guidelines. RESULTS: The selection process yielded 23 studies. Probiotics positively affected depressive symptomatology and anxiety symptoms according to 53.83% and 43.75% of the selected studies, respectively. Among the studies assessing inflammatory biomarkers, 58.31% found they were decreased after administration of probiotics. CONCLUSION: The results emerging from the existing literature about probiotic supplementation for depression treatment are encouraging, but further research is needed considering the shortage of clinical trials on this topic and the heterogeneity of the samples analyzed.
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Unveiling the Connection between Microbiota and Depressive Disorder through Machine Learning.
In the last few years, investigation of the gut-brain axis and the connection between the gut microbiota and the human nervous system and mental health has become one of the most popular topics. Correlations between the taxonomic and functional changes in gut microbiota and major depressive disorder have been shown in several studies. Machine learning provides a promising approach to analyze large-scale metagenomic data and identify biomarkers associated with depression. In this work, machine learning algorithms, such as random forest, elastic net, and You Only Look Once (YOLO), were utilized to detect significant features in microbiome samples and classify individuals based on their disorder status. The analysis was conducted on metagenomic data obtained during the study of gut microbiota of healthy people and patients with major depressive disorder. The YOLO method showed the greatest effectiveness in the analysis of the metagenomic samples and confirmed the experimental results on the critical importance of a reduction in the amount of Faecalibacterium prausnitzii for the manifestation of depression. These findings could contribute to a better understanding of the role of the gut microbiota in major depressive disorder and potentially lead the way for novel diagnostic and therapeutic strategies.
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Microbiota matters: a cross-sectional study protocol for mapping gut microbiome diversity in Malaysian major depressive disorder cases.
INTRODUCTION: Mental health is now recognised as a major global concern affecting people from diverse backgrounds. There is growing evidence that the gut microbiota plays a crucial role by producing metabolites that significantly influence a person's mood and behaviour. Despite its importance, there is a significant gap in the profiling and understanding of the gut microbiota's influence on mental health among Malaysians. Therefore, this study aims to determine gut microbiome profiles among patients with major depressive disorders (MDD) of different treatment groups attending psychiatric clinics in the state hospitals and compare them to healthy individuals in the community of Klang Valley, Malaysia. METHODS AND ANALYSIS: This cross-sectional study will be carried out in Klang Valley, Malaysia. Eligibility of the patients will be assessed by the psychiatrists prior to recruitment of patients. Patients with MDD will be categorised into monotherapy and polypharmacy while healthy individuals will be used as a comparison group. Demographic data will be recorded. Stool samples will be subjected to DNA extraction and 16S rRNA gene-sequencing analysis to determine the microbial compositions of the gut microbiome. ETHICS AND DISSEMINATION: This study will be conducted following the procedure set by the National Medical Research Register Malaysia. The Medical Research Ethics Committee (MREC), Ministry of Health Malaysia, has ratified this study and granted ethical approval to conduct this study (NMRR ID-22-00893-JVW). All the participants will be given an information sheet and will sign a consent form to participate. Participants have the right to withdraw from the study at any time without an explanation. All information gathered will be used for research purposes only and treated as confidential. The results will be submitted to peer-reviewed journals for publication as well as presented at national and international conferences. Informing policy makers at all levels is a crucial aspect of the dissemination and will be done from local to international levels. TRIAL REGISTRATION NUMBER: This study was registered under National Medical Research Register Malaysia (NMRR ID-22-00893-JVW), a mandatory procedure of the Ministry of Health Malaysia before the start of a research.
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Effectiveness of probiotic supplementation in managing depressive symptoms and inflammatory status in patients with depression: A systematic review and meta-analysis.
BACKGROUND AND AIMS: Depression is a multifactorial disorder influenced by genetic, biochemical, psychological, and environmental factors, and it significantly impacts quality of life. Probiotics, especially Lactobacillus and Bifidobacterium strains, have been proposed as adjunct therapies due to their capacity to modulate gut microbiota and the gut-brain axis. This systematic review and meta-analysis aimed to evaluate the effectiveness of probiotic supplementation on depressive symptoms and inflammatory status in individuals with depression. METHODS: Articles were identified through searches in databases including PubMed, Scopus, CINAHL, and Zenodo, using terms related to depression, microbiome, and probiotics. The search, conducted between January and February 2025, yielded 780 articles. After removing duplicates and applying eligibility criteria, 13 studies were included in the systematic review and 7 in the meta-analysis. RESULTS: Probiotic supplementation was significantly associated with improvement in depressive symptoms (p < 0.00001). However, no significant changes were found in inflammatory biomarkers, including interleukin-6 (p = 0.45) and tumor necrosis factor-alpha (p = 0.21). CONCLUSIONS: These results suggest that probiotics may help alleviate depressive symptoms, although their effect on inflammation remains uncertain. Further high-quality studies are necessary to clarify underlying mechanisms and determine the clinical relevance of probiotics as adjunctive therapy in depression..
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Chronic stress leading gut microbiota dysbiosis and neuroinflammation promoted depressive disorder.
Chronic stress was known to contribute to gut microbiota dysbiosis and central neuroinflammation, yet the underlying mechanisms remain poorly understood. In this study, forty-eight male C57BL/6 mice were randomly assigned to three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with probiotic intervention. Mice in the CUMS group were exposed to four weeks of unpredictable stressors, while those in the probiotic group received oral administration of Bifidobacterium triple viable capsules during the stress period. Behavioral assessments revealed pronounced depression-like behaviors in CUMS mice, which were significantly ameliorated by probiotic treatment. 16S rRNA sequencing demonstrated that CUMS reduced gut microbial α-diversity, altered β-diversity, elevated the Firmicutes/Bacteroidetes ratio, and decreased beneficial genera such as Bifidobacterium and Lactobacillus, while increasing the abundance of Escherichia. Probiotic supplementation effectively restored these microbial alterations to near-control levels. Intestinal barrier function was compromised in CUMS mice, as indicated by reduced proteins ZO-1 and Occludin, which partially reversed by probiotic treatment. In the hippocampus and prefrontal cortex, CUMS increased the levels of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and upregulated microglial activation markers (Iba-1, iNOS, and COX-2) in the hippocampus. Probiotic intervention markedly suppressed these neuroinflammatory responses. Moreover, hippocampal CA1 neurons in CUMS mice exhibited structural disorganization, neuronal loss, and nuclear pyknosis, all of which were alleviated by probiotic administration. Collectively, these findings suggest that chronic stress disrupts the gut microbiota-gut-brain axis via microbial dysbiosis and intestinal barrier impairment, thereby promoting neuroinflammation and behavioral abnormalities.
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Effect of probiotics on depressive symptoms: A meta-analysis of human studies.
Accumulating data show that probiotics may be beneficial in reducing depressive symptoms. We conducted an updated meta-analysis and evaluated the effects of probiotics on depressive symptoms. A systematic search of six databases was performed, and the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses, with the priori-defined protocol registered at PROSPERO (CRD42018107426). In total, 19 double-blind, randomized, placebo-controlled trials with a total of 1901 participants were included in the qualitative synthesis. Participants treated with probiotics showed significantly greater improvement in depressive symptoms than those receiving placebo. The clinical population was stratified by clinical diagnosis into those with major depressive disorder (MDD) and those with other clinical conditions. The beneficial effect of probiotics on depressive symptoms was significant in patients with MDD, but not in those with other clinical conditions and in the general population. In addition, multiple strains of probiotics were more effective in reducing depressive symptoms. In conclusion, altering the gut-brain axis with probiotics may be an approach to improve depression severity. It is essential to verify the efficacy of specific combinations or strains of probiotics for depressive symptoms by conducting studies with a larger sample size in the future.
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Changes of gut microbiota reflect the severity of major depressive disorder: a cross sectional study.
Disturbed gut microbiota is a potential factor in the pathogenesis of major depressive disorder (MDD), yet whether gut microbiota dysbiosis is associated with the severity of MDD remains unclear. Here, we performed shotgun metagenomic profiling of cross-sectional stool samples from MDD (n = 138) and healthy controls (n = 155). The patients with MDD were divided into three groups according to Hamilton Depression Rating Scale 17 (HAMD-17), including mild (n = 24), moderate (n = 72) and severe (n = 42) individuals, respectively. We found that microbial diversity was closely related to the severity of MDD. Compared to HCs, the abundance of Bacteroides was significantly increased in both moderate and severe MDD, while Ruminococcus and Eubacterium depleted mainly in severe group. In addition, we identified 99 bacteria species specific to severity of depression. Furthermore, a panel of microbiota marker comprising of 37 bacteria species enabled to effectively distinguish MDD patients with different severity. Together, we identified different perturbation patterns of gut microbiota in mild-to-severe depression, and identified potential diagnostic and therapeutic targets.
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Effect of Probiotic Supplementation on Gut Microbiota in Patients with Major Depressive Disorders: A Systematic Review.
There is accumulating evidence on the beneficial effects of probiotic supplementation for patients with depressive disorders. However, prior reviews on the topic have largely focused on clinical effectiveness with limited emphasis on the underlying mechanisms of action and effects of probiotics on gut microbiota. In accordance with PRISMA guidelines, a systematic literature search of Medline, EMBASE and the Cochrane Library using combinations of the key words, ("depress*" OR "MDD" OR "suicide"), ("probiotic" OR "Lactobacillus" OR "Bifidobacterium") AND ("gut" OR "gut micr*" OR "microbiota"), as well as grey literature was performed. We found seven clinical trials involving patients with major depressive disorder (MDD). The small number of studies and heterogeneous sources of data precluded meta-analysis. Most trials (other than one open-label trial) had a low-to-moderate risk of bias, which was largely due to a lack of control for the effects of diet on gut microbiota. Probiotic supplementation yielded only modest effects on depressive symptoms and there were no consistent effects on gut microbiota diversity, and in most instances, no significant alterations in gut microbiota composition were observed after four to eight weeks of probiotic intervention. There is also a lack of systematic reporting on adverse events and no good longer-term data. Patients with MDD may require a longer time to show clinical improvement and the microbial host environment may also need longer than eight weeks to produce significant microbiota alterations. To advance this field, further larger-scale and longer-term studies are required.
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The intestinal microbiota as a predictor for antidepressant treatment outcome in geriatric depression: a prospective pilot study.
OBJECTIVES: (1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression. DESIGN: Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958). SETTING: Los Angeles, CA, USA (2016-2018). PARTICIPANTS: Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female. INTERVENTION: Levomilacipran (LVM) or placebo. MEASUREMENTS: Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses. RESULTS: Baseline microbiota showed no community level α-diversity or β-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters. CONCLUSIONS: This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.
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Regulatory effects of Lactobacillus zhachilii HBUAS52074T on depression-like behavior induced by chronic social defeat stress in mice: modulation of the gut microbiota.
The gut microbiome has emerged as a growing focus of research and public health interest, leading to the frequent exploration of probiotic dietary supplements as potential treatments for various disorders, such as anxiety and depression. In the present report, changes in inflammation and microbiome composition were assessed in model mice exhibiting depressive-like behaviors that were exposed to the probiotic Lactobacillus zhachilii HBUAS52074T. It was found that L. zhachilii HBUAS52074T alleviated the severity of depressive-like behaviors while increasing serum 5-HT concentrations. Moreover, L. zhachilii HBUAS52074T modulated the composition of the gut microbiota, resulting in a decrease in the abundance of Prevotella and an increase in the abundance of Lactobacillus. Additionally, supplementation with L. zhachilii HBUAS52074T enhanced intestinal barrier function and reduced inflammation in peripheral blood, as well as in the hippocampal and prefrontal cortical tissues. Correlational analyses indicated that the abundance of Lactobacillus was positively correlated with the social interaction ratio, time spent in the center, entries into the center, as well as serum 5-HT and serum IL-10 levels but negatively correlated with immobility time. Overall, chronic social defeat stress was found to be associated with inflammation and the exacerbation of depressive-like behaviors. The above findings suggested that L. zhachilii HBUAS52074T supplementation was sufficient to alter the parameters. Collectively, these data suggest that L. zhachilii HBUAS52074T, derived from naturally fermented foods, may possess therapeutic potential for the treatment of depression.