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Heart rate variability, daily cortisol indices and their association with psychometric characteristics and gut microbiota composition in an Italian community sample.
The microbiota-gut-brain axis is a complex communication system that plays a crucial role in influencing various aspects of our physical and mental health. The goal of this study was to determine the extent to which individual differences in resting measures of vagally-mediated heart rate variability (HRV) and cortisol levels were associated with psychometric and specific gut microbiota characteristics in seventy-five (38 females) healthy individuals. Participants were assessed for vagally-mediated HRV, daily salivary cortisol levels, psychometric characteristics, and gut microbiota composition. Using a categorical approach based on the median split of HRV and cortisol values, we identified an association between low vagally-mediated HRV, greater depressive symptomatology, and altered gut microbiota (e.g., a higher abundance of Prevotella and a smaller abundance of Faecalibacterium, Alistipes, and Gemmiger). This suggests that vagally-mediated HRV may be a useful biomarker of microbiota-gut brain axis function, and that low vagally-mediated HRV may play an important role in the bidirectional link between gut dysbiosis and depression. On the other hand, daily cortisol parameters (e.g., cortisol awakening response, diurnal cortisol slope) were associated either with higher anxiety and perceived stress, or with a specific gut microbiota profile. Therefore, their utility as biomarkers of microbiota-gut-brain axis function needs further scrutiny.
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Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by remodeling gut microbiota and regulating host metabolism.
AIMS: There is growing evidence that the gut microbiota plays a significant part in the pathophysiology of chronic stress. The dysbiosis of the gut microbiota closely relates to dysregulation of microbiota-host cometabolism. Composition changes in the gut microbiota related to perturbations in metabolic profiles are vital risk factors for disease development. Hyperbaric oxygen therapy is commonly applied as an alternative or primary therapy for various diseases. Therefore, a metabolic and gut bacteria perspective is essential to uncover possible mechanisms of chronic stress and the therapeutic effect of hyperbaric oxygenation. We determined that there were significantly disturbed metabolites and disordered gut microbiota between control and chronic stress group. The study aims to offer further information on the interactions between host metabolism, gut microbiota, and chronic stress. METHODS: At present, chronic unpredictable mild stress is considered the most widespread method of modeling chronic stress in animals, so we used a chronic unpredictable mild stress mouse model to characterize changes in the metabolome and microbiome of depressed mice by combining 16S rRNA gene sequencing and UHPLC-MS/MS-based metabolomics. Pearson's correlation-based clustering analysis was performed with above metabolomics and fecal microbiome data to determine gut microbiota-associated metabolites. RESULTS: We found that 18 metabolites showed a significant correlation with campylobacterota. Campylobacterota associated metabolites were significantly enriched mainly in the d-glutamate and d-glutamine metabolism. Hyperoxia treatment may improve depression-like behaviors in chronic stress model mice through regulating the disrupted metabolites. CONCLUSIONS: Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by remodeling Campylobacterota associated metabolites.
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A microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression reveals physiological characteristics similar to depression.
The diverse commensal microbiome of the human intestine has been considered to play a central role in depression. However, no host-microbiota co-culture system has been developed for depression, which hinders the controlled study of the interaction between depression and gut microbiota. We designed and manufactured a microfluidic-based gut-on-a-chip model containing the gut microbiota of patients with depression (depression-on-gut-chip, DoGC), which enables the extended co-culture of viable aerobic human intestinal epithelial cells and anaerobic gut microbiota, and allows the direct study of interactions between human gut microbiota and depression. We introduced representative gut microbiota from individuals with depression into our constructed DoGC model, successfully recapitulating the gut microbiota structure of depressed patients. This further led to the manifestation of physiological characteristics resembling depression, such as reduced gut barrier function, chronic low-grade inflammatory responses and decreased neurotransmitter 5-HT levels. Metabolome analysis of substances in the DoGC revealed a significant increase in lipopolysaccharides and tyrosine, while hyodeoxycholic acid, L-proline and L-threonine were significantly reduced, indicating the occurrence of depression. The proposed DoGC can serve as an effective platform for studying the gut microbiota of patients with depression, providing important cues for their roles in the pathology of this condition and acting as a powerful tool for personalized medicine.
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The Intervention of Prebiotics on Depression via the Gut-Brain Axis.
The imbalance of intestinal microbiota can cause the accumulation of endotoxin in the main circulation system of the human body, which has a great impact on human health. Increased work and life pressure have led to a rise in the number of people falling into depression, which has also reduced their quality of life. The gut-brain axis (GBA) is closely related to the pathological basis of depression, and intestinal microbiota can improve depressive symptoms through GBA. Previous studies have proven that prebiotics can modulate intestinal microbiota and thus participate in human health regulation. We reviewed the regulatory mechanism of intestinal microbiota on depression through GBA, and discussed the effects of prebiotics, including plant polysaccharides and polyphenols on the regulation of intestinal microbiota, providing new clues for the prevention and treatment of depression.
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Association between Fecal Microbiota, SCFA, Gut Integrity Markers and Depressive Symptoms in Patients Treated in the Past with Bariatric Surgery-The Cross-Sectional Study.
(1) Background: Depressive symptoms often appear after surgical treatment. (2) Methods: We involved 41 adults who underwent bariatric surgery a minimum of 6 months before the study and had the Beck scale ≥12. We analysed patients' mental state, gut barrier markers, faecal short chain fatty acids, and microbiota. (3) Results: Gut microbiota composition differed significantly among patients undergoing two different types of surgery (F = 1.64, p = 0.00002). Additionally, we discovered an association between short chain fatty acids and the Beck scale (F = 1.22, p = 0.058). The rearrangement of bacterial metabolites may be due to the patients' use of increased dietary protein, with insufficient intake of products containing vegetable fiber (Diet Quality Index (DQI-I )adequacy 22.55 (±3.46) points). (4) Conclusions: Bariatric surgery affects the gut microbiota, which may play an important role in the development of depressive and gastrointestinal symptoms in patients after bariatric surgery. Low fiber consumption and increased levels of faecal isobutyric acid may lead to intestinal inflammation. There is a need for further research on this topic including a larger sample size.
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Mood and Microbes: Gut to Brain Communication in Depression.
The gut microbiota, acting via the gut-brain axis, modulates key neurobiological systems that are dysregulated in stress-related disorders. Preclinical studies show that the gut microbiota exerts an influence over neuroimmune and neuroendocrine signaling pathways, in addition to epigenetic modification, neurogenesis, and neurotransmission. In humans, preliminary evidence suggests that the gut microbiota profile is altered in depression. The full impact of microbiota-based treatments, at different neurodevelopmental time points, has yet to be fully explored. The integration of the gut microbiota, as a mediator, in the complex trajectory of depression, may enhance the possibility of personalized precision psychiatry.
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Combined Administration of Lactobacillus or Bifidobacterium Offers Enhanced Antidepressant and Anxiolytic Activity in a Dose Dependent Manner.
PURPOSE: Gut microbiota is strongly linked to the activity of the bidirectional gut-brain axis, which influences neuropsychological processes at multiple levels. Changes in the gut microbiota have been implicated in mood disorders, and probiotics have been explored for their ability to mitigate the effects of stress on mental health. Here, we investigated the therapeutic benefits of different concentrations and combinations of Lactobacillus and Bifidobacterium in a mouse model of stress induced depression and anxiety. METHODS: Sixty-three male ICR mice (6-8 weeks old; 20-25g) divided into nine groups were used for this study. The test groups underwent chronic unpredictable mild stress protocols for two weeks before receiving low (104 CFU/ml) or high (108 CFU/ml) doses of either monotherapy (Lactobacillus or Bifidobacterium) or a combination therapy (Lactobacillus and Bifidobacterium) for four weeks. The antidepressant, fluoxetine, served as the positive control. Measurements of weight and sucrose preference were performed at four time points in addition to a battery of behavioral tests (open field tests, forced swim test, tail suspension test, and hot plate test) at the endpoint to assess depression and anxiety-like behavior. RESULTS: Low doses of the probiotic formulation (mono- or combined therapy) reversed weight loss but not anhedonia. In contrast, high doses of probiotic formulations (mono- or combined therapy), along with fluoxetine, were effective in reversing the weight loss and anhedonia caused by chronic unpredictable mild stress. Probiotics ameliorated stress-induced immobility as measured by both the forced swim and tail suspension tests, while also reducing anxiety-like behavior (increased peripheral activity) in the open field test. High doses of mono- or combined therapy increased curling behavior in the tail suspension test, whereas fluoxetine failed to do so. CONCLUSION: This study indicates the species- and dose-dependent beneficial effects of probiotics on behavioral outcomes associated with depression while also reversing weight loss. Evidence suggests that probiotics and fluoxetine may exert antidepressant activity via different mechanisms.
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Influence of early life stress on depression: from the perspective of neuroendocrine to the participation of gut microbiota.
Depression is the most common mental disorder and has become a heavy burden in modern society. Clinical studies have identified early life stress as one of the high-risk factors for increased susceptibility to depression. Alteration of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress is one of the key risk factors for depression susceptibility related to early life stress. Laboratory animal studies have demonstrated that maternal separation (MS) for extended periods elicits HPA axis changes. These changes persist into adulthood and resemble those present in depressed adult individuals, including hyperactivity of the HPA axis. In addition, there is growing evidence that inflammation plays an important role in depression susceptibility concerned with early life stress. Individuals that have experienced MS have higher levels of pro-inflammatory cytokines and are susceptible to depression. Recently, it has been found that the gut microbiota plays an important role in regulating behavior and is also associated with depression. The translocation of gut microbiota and the change of gut microbiota composition caused by early stress may be a reason. In this review, we discussed the mechanisms by which early life stress contributes to the development of depression in terms of these factors. These studies have facilitated a systematic understanding of the pathogenesis of depression related to early life stress and will provide new ideas for the prevention and treatment of depression.
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Effects of microbiota-based interventions on depression and anxiety in children and adolescents-A systematic review.
This study aims to systematically review evidence on gut microbiota-based interventions for reducing depression- and anxiety-like symptoms in children and adolescents with autism spectrum disorder, irritable bowel syndrome, Prader-Willi syndrome, below-average literacy skills or anorexia nervosa, where some individuals may exhibit indicators of depression or anxiety. This review includes evaluated evidence from randomized controlled trials (RCTs) involving children and adolescents aged 3-19 years, identified from PsycINFO, Medline (Ovid version), Web of Science, and the reference lists of existing reviews. Risk of bias were assessed using Risk of Bias Tool (RoB 2) in RevMan (version 5.4, Cochrane Collaboration). The results were qualitatively summarized by describing the main findings across the studies. Of the 1561 studies screened, 10 RCTs with 408 participants were included. Three gut microbiota-based interventions evaluated were probiotics, prebiotics, and dietary supplementation. Probiotics and dietary supplementation were identified as effective on reducing depression and anxiety in three studies; no significant effects were reported in the remaining seven studies. No evidence supported the effectiveness of prebiotics in reducing depression and anxiety in children and adolescents. Four studies presented low risk of bias, while others showed some bias in the randomization process, allocation concealment, selective reporting, and blinding of the outcome assessment. This review highlights the potential of probiotics and dietary supplements in treating depression and anxiety in children and adolescents. However, the current evidence is constrained by inadequate mental health measurements, participant heterogeneity, and small sample sizes in reviewed studies. Further well-designed studies are needed to confirm their effectiveness.
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Gut feelings: Dysbiosis of gut microbiota and short-chain fatty acids associated with prenatal depression, pregnancy-related anxiety, and prenatal combined depression and anxiety.
OBJECTIVES: The role of the gut microbiota and short-chain fatty acids (SCFAs) in psychiatric disorders in pregnant women has not been fully elucidated. Therefore, this study aimed to investigate the association between the gut microbiota and its metabolite SCFAs and prenatal depression, pregnancy-related anxiety, and prenatal combined depression and anxiety. METHODS: In total 200 pregnant women in the third trimester were recruited for this study. The Edinburgh Postnatal Depression Scale and Pregnancy-Related Anxiety Questionnaire Revised-2 were used to evaluate pregnant women's anxiety and depression, and stool samples were collected for gut microbiome and SCFAs. RESULTS: This study found that reduced abundance of Allobaculum and Cetobacterium were associated with pregnancy-related anxiety in women. Furthermore, the enrichment of Anaerofustis, Gemella, and Staphylococcus and the reduction of Tyzzerella and unclassified_f_UCG-011 were associated with prenatal depression. This study was the first to indicate that women with comorbid prenatal anxiety and depression share similarities in gut microbiota and SCFAs with women with prenatal depression (Anaerofustis, Gemella, Staphylococcus, Tyzzerella, and isohexanoic acid). This study also found that certain gut microbial profiles were associated with prenatal comorbid anxiety and depression. While receiver operating characteristic analysis suggests a limited ability of the gut microbiota alone to predict prenatal psychological distress problems, the integration of phenotypic variables into the model significantly improved the model's predictive ability. CONCLUSION: Our findings suggested that dysbiosis of gut microbiota and SCFAs are associated with prenatal psychiatric disorders. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing prenatal psychiatric disorders.