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[Depressive Disorder and Gut-brain Interaction].
Depressive disorder is a stress-induced condition, which has been suggested to have bidirectional interactions with the gut microbiota. Probiotics such as Bifidobacterium and Lactobacillus have been suggested to mitigate stress response. Irritable bowel syndrome (IBS) is a typical phenotype of psychological distress manifested in the gastrointestinal system, and often develops in patients with depressive disorder. The altered gut microbiota and resultant inflammation in the gut play an important role in at least a portion of IBS. Animal models of depression have shown abnormalities in the gut such as increased gut permeability, and the probiotics ameliorate their chronic depression-like behaviors and altered stress responses. There have been only a few studies that have directly investigated the gut microbiota in patients with depression. We reported results suggesting that individuals with lower bacterial counts for Bifidobacterium and/or Lactobacillus are more common in patients with major depressive disorder than in healthy controls. the collectively use of gut microbiota in the diagnosis and treatment of depressive disorder seems to be a promising approach.
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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.
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Personalized Nutrition for Depression: Impact on the Unholy Trinity.
Major depressive disorder (MDD) is a chronic affective disorder that has a strong neuroinflammatory component underpinning its etiology. Recent studies indicate that MDD is also associated with changes in the gut microbiota and that the latter is mainly modulated by diet. Microbiota-based personalized nutrition aims to provide an individual-specific diet that will yield the maximum benefit from a given diet since the gut microbiota is accounted for the variations that individuals present in response to a given food. In this review, we present and discuss 5 possible outcomes of using microbiota-based personalized nutrition. Harnessing this approach is essential to design more accurate therapies to prevent and treat MDD or to even help in drug metabolism, especially in the case of antidepressants.
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Association between dietary patterns and suicide ideation among depressed adults: Insights from NHANES 2007-2020.
BACKGROUND: Dietary patterns are strongly linked to the risk of major depressive disorder (MDD). However, research on the relationship between dietary patterns and MDD with suicidal ideation (MDD + SI) are limited. The Healthy Eating Index (HEI)-2015, Dietary Inflammatory Index (DII), Comprehensive Dietary Antioxidant Index (CDAI), Oxidative Balance Score (OBS), and Dietary Index for Gut Microbiota (DI-GM) are five validated tools for assessing dietary patterns based on inflammation, antioxidant capacity, and gut microbiota diversity. This study aims to investigate the association between these dietary indices and MDD + SI. METHODS: A total of 23,621 participants from the 2007-2020 National Health and Nutrition Examination Survey were included in this study. MDD and SI were assessed using the PHQ-9. Weighted multivariable logistic regression, subgroup analyses, and restricted cubic spline (RCS) models were applied to analyze the relationships between five dietary indices and the risks of MDD and MDD + SI. RESULTS: All five dietary indices showed associations with MDD to varying degrees; however, only DI-GM exhibited a significant negative association with MDD + SI after adjustment for confounding factors. Subgroup and stratified linear trend analyses revealed that this association was stronger among former smokers, obese individuals and those with hypertension or diabetes. RCS analysis showed a significant non-linear relationship between DI-GM and MDD, while a significant linear dose-response relationship was observed for DI-GM and MDD + SI. LIMITATIONS: Cross-sectional study designs cannot establish causality. CONCLUSION: The findings of this study revealed a significant association between DI-GM and MDD + SI. Dietary interventions that promote gut microbiota diversity may help reduce the risk of MDD + SI.
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6'-Sialyllactose alleviates loperamide-induced constipation and depressive-like behaviors in mice by modulating gut microbiota and short-chain fatty acids.
Constipation is a common gastrointestinal disorder, which impairs the quality of life. This study investigated the ameliorative effects of 6'-sialyllactose (6'-SL) in a loperamide-induced murine model of constipation and associated depressive-like behaviors. Constipation was induced in mice by loperamide and subsequently treated by administering 6'-SL at doses of 100 or 300 mg per kg body weight for 14 days. The ameliorative effects of 6'-SL were evaluated through defecation-related parameters, histopathological and immunohistochemical analyses of colonic and hippocampal tissues, biochemical assays, behavioral tests, gut microbiota analysis, and short-chain fatty acid (SCFA) levels. The results showed that 6'-SL alleviated loperamide-induced constipation by improving defecation-related parameters, colonic histopathology, gastrointestinal neurotransmitter levels, and AQP3 and SCF/c-Kit levels. Moreover, 6'-SL ameliorated constipation-associated depressive-like behaviors and hippocampal alterations while modulating the gut microbiota composition and increasing the SCFA levels. Spearman's correlation analysis suggested that the alleviation of constipation and depressive-like behaviors may be associated with alterations in the gut microbiota and SCFA levels upon 6'-SL intervention. These results provide a theoretical and practical basis for developing functional foods and biomedical products based on 6'-SL.
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Metagenomic analysis of the gut microbiota in major depressive disorder with different antidepressant efficacy: A prospective cohort study.
BACKGROUND: Major depressive disorder (MDD) is globally prevalent, with Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) as first-line treatment. However, 30 %-40 % of patients have inadequate response, and early identification is difficult. Gut microbiota contributes to MDD pathogenesis through the gut-brain axis, but baseline differences between responders and non-responders to SSRIs or SNRIs remain unclear. METHODS: 82 MDD individuals were initially screened. However, due to issues with the drug administration and fecal sample availability, a total of 43 people were eventually included. Based on 3-month Hamilton Depression Rating Scale (HAMD-17) changes, 29 patients were responders (39.12 ± 15.79 years, 8 males), while 14 were non-responders (40.14 ± 17.28 years, 5 males). Baseline assessments encompassed Depression Anxiety scales, demographics, and fecal metagenomic analysis (taxonomic/functional annotation, and differential analysis of microbial species and pathways). RESULTS: Baseline demographic characteristics, lifestyle factors, and anxiety/depression scores were comparable. Non-responders had higher relative abundances of Bacteroidaceae and Bacteroide; LEfSe showed responders enriched Hungatella, Ligilactobacillus_ruminis, and non-responders enriched Anaerostipes, Bacteroides_faecis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis identified 246 differentially expressed KEGG Orthologies and 13 pathways, with the steroid biosynthesis pathway (map00100) being enriched in non-responders and the D-amino acid metabolism pathway (map00470) enriched in responders. The study has limitations: small sample size and it lacks direct mechanism validation. CONCLUSIONS: The composition and functional pathways of gut microbiota exhibit significant differences between responders and non-responders to SSRIs or SNRIs among MDD patients, providing clues for the development of new treatment strategies.
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Gut microbiota variations in patients diagnosed with major depressive disorder-A systematic review.
OBJECTIVE: The etiology of major depressive disorder (MDD) is multi-factorial and has been associated with a perturbed gut microbiota. Thus, it is therefore of great importance to determine any variations in gut microbiota in patients with MDD. METHODS: A systematic literature search was conducted including original research articles based on gut microbiota studies performed in patients with MDD. Demographic and clinical characteristics, applied methodology and observed gut microbiota composition were compared between included studies. RESULTS: Seventeen studies were included with a total of 738 patients with MDD and 782 healthy controls using different DNA purification methods, sequencing platforms and data analysis models. Four studies found a reduced α-diversity in patients with MDD, while gut microbiota compositions clustered separately according to β-diversity between patients and controls in twelve studies. Additionally, there was an increase in relative abundance of Eggerthella, Atopobium, and Bifidobacterium and a decreased relative abundance of Faecalibacterium in patients with MDD compared with healthy controls. CONCLUSION: Gut microbiota differs significantly when comparing patients with MDD and healthy controls, though inconsistently across studies. The heterogeneity in gut microbiota compositions between the studies may be explained by variations in study design.
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Integrated Microbiome and Metabolomic Profiling to Identify Potential Biomarkers of Major Depressive Disorder.
The pathophysiology of major depressive disorder (MDD) remains incompletely understood, hindering the development of objective diagnostic markers. While the microbiota-gut-brain axis is implicated in MDD, the functional link between gut dysbiosis and systemic metabolism remains largely obscure. To address this, we employed an integrated multi-omics approach combining 16S rRNA gene sequencing, GC-MS analysis of urine and plasma, complemented by UPLC-QTOF-MS profiling of plasma, in a Korean cohort (n = 69). We identified distinct taxonomic shifts, specifically the enrichment of the Eubacterium eligens group and Veillonella in MDD patients. Integrated correlation analysis revealed a functional "gut-lipid axis", where these taxa were strongly associated with alterations in host acylcarnitine and fatty acid metabolism. Notably, diagnostic evaluation demonstrated that the plasma metabolic profile yielded superior predictive accuracy (AUC = 0.862) compared to the gut microbiota (AUC = 0.654). Our findings suggest that while the gut microbiome provides mechanistic insights into lipid dysregulation, the circulating metabolome serves as a more robust, proximal diagnostic readout for MDD.
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Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?
Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.
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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.