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Landscape of gut microbiota and metabolites and their interaction in comorbid heart failure and depressive symptoms: a random forest analysis study.
There is increasing evidence that alterations in gut microbial composition and function are associated with cardiovascular or psychiatric disease. Therefore, it is meaningful to investigate the taxonomic and functional characterization of the microbiota in HF patients who also have depressive symptoms. In this cross-sectional study, Cloacibacillus and alpha-tocopherol were determined as new diagnostic markers. Furthermore, intestinal microecosystem disorders are closely linked to depressive symptoms in HF patients, providing a new reference viewpoint for understanding the gut-heart/brain axis.
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Mitochondria could be a potential key mediator linking the intestinal microbiota to depression.
The intestinal microbiota has been reported to affect depression, a common mental condition with severe health-related consequences. However, what mediates the effect of the intestinal microbiota on depression has not been well elucidated. We summarize the roles of the mitochondria in eliciting beneficial effects on the gut microbiota to ameliorate symptoms of depression. It is well known that mitochondria play a key role in depression. An important pathogenic factor, namely inflammatory response, may adversely impact mitochondrial functionality to maintain cellular homeostasis. Dysfunction of mitochondria not only affects neuronal function but also reduces neuron cell numbers. We posit that the intestinal microbiota could affect neuronal mitochondrial function through short-chain fatty acids such as butyrate. Brain inflammatory processes could also be affected through the modulation of gut permeability and blood lipopolysaccharide levels. Aberrant mitochondria functionality coupled to adverse cellular homeostasis could be a key mediator for the effect of the intestinal microbiota on the progression of depression.
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Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC/MS-based metabolomics.
As a prevalent, life-threatening and highly recurrent psychiatric illness, depression is characterized by a wide range of pathological changes; however, its etiology remains incompletely understood. Accumulating evidence supports that gut microbiota affects not only gastrointestinal physiology but also central nervous system (CNS) function and behavior through the microbiota-gut-brain axis. To assess the impact of gut microbiota on fecal metabolic phenotype in depressive conditions, an integrated approach of 16S rRNA gene sequencing combined with ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) based metabolomics was performed in chronic variable stress (CVS)-induced depression rat model. Interestingly, depression led to significant gut microbiota changes, at the phylum and genus levels in rats treated with CVS compared to controls. The relative abundances of the bacterial genera Marvinbryantia, Corynebacterium, Psychrobacter, Christensenella, Lactobacillus, Peptostreptococcaceae incertae sedis, Anaerovorax, Clostridiales incertae sedis and Coprococcus were significantly decreased, whereas Candidatus Arthromitus and Oscillibacter were markedly increased in model rats compared with normal controls. Meanwhile, distinct changes in fecal metabolic phenotype of depressive rats were also found, including lower levels of amino acids, and fatty acids, and higher amounts of bile acids, hypoxanthine and stercobilins. Moreover, there were substantial associations of perturbed gut microbiota genera with the altered fecal metabolites, especially compounds involved in the metabolism of tryptophan and bile acids. These results showed that the gut microbiota was altered in association with fecal metabolism in depressive conditions. These findings suggest that the 16S rRNA gene sequencing and LC-MS based metabolomics approach can be further applied to assess pathogenesis of depression.
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Fecal Microbial and Metabolomic Change during treatment course for depression: An Observational Study.
BACKGROUND: There is growing evidence regarding the connection between alterations in gut microbiota and their metabolites in patients with depressive disorders, suggesting a potential role in pathophysiology. Our study aimed to investigate the relationship between microbial, metabolomic features and the course of treatment for depression in a real-world clinical setting. METHODS: Patients diagnosed with depressive disorders were recruited, and their stool was collected at three time points during their depression treatments. Patients were divided into three groups: non-responders, responders, and stable remitters. Gut microbiomes were analyzed using 16S rRNA gene sequencing, and gut metabolomes were analyzed by a mass spectrometry approach. Microbiomes/metabolomes were compared between groups cross-sectionally and longitudinally. RESULTS: A total of 33 patients were recruited and divided into non-responders (n = 16), responders (n = 11), and stable remitters (n = 6). Non-responders presented lower alpha diversity in the Phylogenic Diversity index compared to responders during the treatment course (p = 0.003). Non-responders presented increased estimated glutamate synthesis functions by the microbiota compared to responders and stable remitters (p = 0.035). There were no specific microbiota or metabolome that differentiated the three groups. LIMITATIONS: Small sample size with no healthy controls. CONCLUSIONS: Our results indicate that both cross-sectional microbial features and longitudinal microbial transitions are different depending on the treatment course of depression. Controlled studies, as well as animal studies, are needed in the future to elucidate the causal relationship between microbiota and depression.
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Combating depression with rosemary (Rosmarinus officinalis L.)-derived polyphenols: Major phytochemicals, functional properties, and potential.
Depression is a common mental condition with high prevalence and recurrence rates worldwide. The active polyphenols in Rosmarinus officinalis L. contain several pharmacological activities, including anti-inflammatory, antibacterial, and neuroprotective characteristics. However, the effects of rosemary polyphenols on depression have not been thoroughly studied. The anti-inflammatory activity and regulatory effects on gut microbiota of key rosemary polyphenols, as well as their impacts on depression, are the main emphasis of this research. We conclude that the anti-depressive effects of rosemary polyphenols are due to anti-inflammatory properties and bidirectional relationship with gut microbiota, including inhibiting inflammatory pathways and cytokines (reducing pro-inflammation cytokines, suppressing NF-κB and NLRP3 inflammasomes, and upregulating Nrf2/HO-1 pathway), altering intestinal microbiota structure and metabolites (polyphenols-related microbial metabolites and biotransformation of polyphenols by microbiota). This paper provides a better understanding of the anti-depressive effects of polyphenols in Rosmarinus officinalis L.
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The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.
BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms. METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect. RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit. INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered. STUDY REGISTRATION: PROSPERO no. 143178.
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Synergistic efficacy of inulin gel capsulated metal-phenolic networks: Treating colitis and depression by regulating AKK and gut-brain axis.
Inflammatory bowel disease (IBD) is a chronic immune-mediated condition affecting the intestinal tract. Though conventional therapies aim to control symptoms and induce remission, their long-term use is hindered by systemic side effects and inadequate efficacy, highlighting the need for safer and more effective treatments. In this study, we developed luteolin-loaded nanoparticles (Lut-NPs) by encapsulating luteolin within metal-phenolic networks (MPNs) formed through coordination between epigallocatechin gallate (EGCG) and Ce3⁺ ions. The resulting Lut-NPs showed excellent biocompatibility, strong antioxidant and anti-inflammatory activities, and remarkable stability under gastrointestinal conditions. To improve intestinal retention, the nanoparticles were incorporated into an inulin-based hydrogel, generating a Lut-NPs/Gel composite system. In a DSS-induced colitis model, oral administration of Lut-NPs/Gel demonstrated significant therapeutic efficacy, including restoration of the intestinal barrier, suppression of pro-inflammatory pathways, and reshaping the gut microbiome. The treatment also promoted macrophage polarization from the M1 to the M2 phenotype. AKK, usually considered beneficial but elevated during inflammation, was restored to normal levels after Lut-Nps/Gel treatment, suggesting its potential as a biomarker of intestinal recovery. Additionally, the treatment alleviated depression-like behaviors via the microbiota-gut-brain axis. Overall, this work provides a safe and promising multifunctional strategy for treating IBD and associated neuropsychiatric symptoms.
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TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis.
BACKGROUND AND PURPOSE: Anxiety and depression have been associated with imbalances in the gut microbiota and bile acid metabolism. Takeda G protein-coupled receptor 5 (TGR5), a bile acid receptor involved in metabolism, is influenced by the gut microbiota. This study aimed to investigate the relationship between anxiety, depression, and microbiota using TGR5 knockout mice. METHODS: We employed the following methods: (1) Assessment of behavioral changes, (2) Measurement of 5-HT levels and protein expression, (3) Analysis of stool samples, (4) Utilization of gene sequencing and statistical analysis to identify microbial signatures, (5) Examination of correlations between microbial signatures and 5-HT levels, and (6) Fecal microbiota transplantation experiments of TGR5-/- mice. RESULTS: The deletion of TGR5 was found to result in increased anxiety- and depression-like behaviors in mice. TGR5 knockout mice exhibited significant reductions in 5-hydroxytryptamine (5-HT) levels in both serum and hippocampus, accompanied by a decrease in the expression of 5-HT1A receptor in the hippocampus. Moreover, TGR5 deficiency was associated with a decrease in the species richness of the gut microbiota. Specifically, the gut microbiota compositions of TGR5 knockout mice displayed distinct differences compared to their littermates, characterized by higher abundances of Anaeroplasma, Prevotella, Staphylococcus, Jeotgalicoccus, and Helicobacter, and a lower abundance of Bifidobacterium. Notably, a strong association between Jeotgalicoccus as well as Staphylococcus and serum 5-HT levels was observed in co-occurrence network. Furthermore, mice that received fecal microbiota transplants from TGR5-/- mice displayed anxiety and depression -like behaviors, accompanied by alterations in 5-HT levels in the hippocampus and serum. LIMITATIONS: Study limitations for gut bacteria were analyzed at the genus level only. CONCLUSION: TGR5 deletion in mice induces anxiety and depression-like behaviors, linked to reduced 5-HT levels in serum and the hippocampus. Gut microbiota changes play a direct role in these behaviors and serotonin alterations. This implicates TGR5 and gut bacteria in mood regulation, with potential therapeutic implications.
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Effects of regulating gut microbiota on the serotonin metabolism in the chronic unpredictable mild stress rat model.
OBJECTIVE: This study was to inspect the antidepressant-like effect of prebiotics and probiotics, and to explore the effect of modulating gut microbiota on the serotonin (5-HT) metabolism. METHODS: Fifty rats were separated into control and other four groups randomly. The four groups underwent the chronic unpredictable mild stress (CUMS) intervention with or without prebiotics and probiotics (Bifidobacterium longum, L. rhamnosus) treatment. After weighted, the animals underwent a series of behavioral tests comprising the sucrose preference test (SPT) and the forced swimming test (FST). Central and colonic serotonin levels and relative metabolism factors were measured and analyzed. Microbiota was examined by 16S rRNA gene pyrosequencing. RESULTS: CUMS intervention caused a decrease in body weight, an increase in FST, and a decrease in SPT. Prebiotics and probiotics all ameliorated the CUMS-induced loss of weight and depressive-like behaviors to a certain extent, especially L. rhamnosus. Compared with the group of CUMS intervention, the rats of probiotics and probiotics treatment had a tendency to reduce colonic 5-HT and increase 5-HT in frontal cortex and hippocampus. However, there was no significant difference in peripheral blood 5-HT among these groups. Furthermore, CUMS caused noteworthy gut microbiota variations at the phylum and other levels in rats. Remarkably, there were considerable relations of perturbed gut microbiota with the changed metabolism of 5-HT. CONCLUSION: In conclusion, these findings implied that prebiotics and probiotics have antidepressive effects, and a considerable effect on the regulation of 5-HT metabolism, especially L. rhamnosus.
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The role of microbiota and inflammation in self-judgement and empathy: implications for understanding the brain-gut-microbiome axis in depression.
RATIONALE: The gut-brain axis includes bidirectional communication between intestinal microbiota and the central nervous system. Bifidobacterium and Lactobacillus spp. have been implicated in psychological health, such as depression, through various pathways (e.g. inflammation). Research needs a better understanding of direct and indirect effects through examination of psychological factors that make people susceptible to, or offer protection against, depression. OBJECTIVE: This study investigated the relationships between gut microbiota, inflammation and psychological risk and resilience factors for depression. METHODS: Forty participants (13 m/27 f) recruited from the general population completed self-report questionnaires for depression, self-judgement, over-identification and affective and cognitive empathy. Faecal and blood samples were taken to assay microbiota (Bifidobacterium; Lactobacillus spp.) and pro-inflammatory molecules (C-reactive protein, CRP and interleukin-6, IL-6), respectively. RESULTS: Hierarchical regression analyses (controlling for sex, age and the shared variance of risk and resilience factors) showed that (i) cognitive depression was significantly predicted by negative self-judgement and reduced cognitive empathy; (ii) abundance of Lactobacillus spp. was directly related to positive self-judgement but only indirectly to cognitive depression and lower affective empathy (both through self-judgement); and (iii) CRP was the strongest predictor of reduced cognitive empathy, with suppression effects seen for age (negative) and IL-6 (positive) after controlling for CRP. CONCLUSIONS: Findings suggest that lactobacilli and inflammation may be differentially associated with mood disorder via brain mechanisms underpinning self-judgement and cognitive empathy, respectively. Further trials investigating interventions to increase Lactobacillus spp. in depression would benefit from direct measures of self-judgement and affective empathic distress, whilst those that aim to reduce inflammation should investigate cognitive empathy.