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Probiotics' Effects in the Treatment of Anxiety and Depression: A Comprehensive Review of 2014-2023 Clinical Trials.
Changes in the gut microbiome can affect cognitive and psychological functions via the microbiota-gut-brain (MGB) axis. Probiotic supplements are thought to have largely positive effects on mental health when taken in sufficient amounts; however, despite extensive research having been conducted, there is a lack of consistent findings on the effects of probiotics on anxiety and depression and the associated microbiome alterations. The aim of our study is to systematically review the most recent literature of the last 10 years in order to clarify whether probiotics could actually improve depression and anxiety symptoms. Our results indicate that the majority of the most recent literature suggests a beneficial role of probiotics in the treatment of depression and anxiety, despite the existence of a substantial number of less positive findings. Given probiotics' potential to offer novel, personalized treatment options for mood disorders, further, better targeted research in psychiatric populations is needed to address concerns about the exact mechanisms of probiotics, dosing, timing of treatment, and possible differences in outcomes depending on the severity of anxiety and depression.
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Adherence to a Mediterranean Diet Predicts Gastrointestinal and Anxiety Symptom Response in Irritable Bowel Syndrome.
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction, and diet plays a key role in management of symptoms. The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has been widely adopted in clinical practice. However, emerging evidence highlights the potential of other diet interventions for IBS. We recently showed in a 6-week randomized controlled trial in 59 patients with IBS and anxiety or depression symptoms that a Mediterranean diet (MD), rich in whole-grain cereals, vegetables, legumes, fruit, fish and olive oil, was feasible and reduced gastrointestinal (GI) and psychological symptom severity compared with habitual diet controls.1 The gut, mental, and broader health benefits of an MD are proposed to be driven by its enrichment of the microbiome.2.
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Early-life gastrointestinal inflammation and the developing brain: Unravelling the pathways to long-term cognitive dysfunction.
The gut-brain axis (GBA) is a complex, bidirectional communication network critical to integrating central nervous system functions with gastrointestinal (GI) health. This review examines how disruptions to the GBA during the critical early-life developmental window - a period of rapid neurogenesis and microbial colonization - contribute to long-term neurocognitive and psychiatric vulnerabilities. Evidence from animal models demonstrates that early-life stress, antibiotics, and infection induce sustained neuro-inflammation and alter microglial function, leading to long-term behavioral and cognitive impairments in adulthood. Human studies corroborate these findings, revealing that severe early GI insults, such as necrotizing enterocolitis, confer a high risk (40%) of global neurodevelopmental impairment and specific attention deficits. Chronic inflammatory conditions similarly impact the central nervous system: A high burden of early severe enteric infection is an independent risk factor for diminished intelligence quotient (IQ) and executive function, while conditions like celiac disease and inflammatory bowel disease are associated with persistent deficits in attention, processing speed, memory, and executive function. These clinical outcomes are strongly linked to systemic inflammation [elevated interleukin-6, kynurenine-to-tryptophan (Kyn:Trp) ratio], micronutrient deficiencies (iron, vitamin B12, folate), and structural white matter changes in the brain. Furthermore, chronic GI disease imposes a significant psychiatric burden, with high comorbidity of anxiety and depression often mediating poor health-related quality of life, particularly in pediatric inflammatory bowel disease. The findings underscore the necessity for a shift in clinical practice: Chronic GI disease in early life must be recognized as a red flag for neurocognitive risk. We advocate for a multidisciplinary approach encompassing early neurodevelopmental follow-up for high-risk groups and routine screening for cognitive and emotional comorbidities. Future research must focus on long-term prospective cohorts, identifying precise mechanistic biomarkers (metabolomics, microbiome signatures), and conducting interventional trials targeting the GBA to mitigate these long-term functional consequences.
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High cholesterol intake remodels cholesterol turnover and energy homeostasis in Nile tilapia (Oreochromis niloticus).
UNLABELLED: The roles of dietary cholesterol in fish physiology are currently contradictory. The issue reflects the limited studies on the metabolic consequences of cholesterol intake in fish. The present study investigated the metabolic responses to high cholesterol intake in Nile tilapia (Oreochromis niloticus), which were fed with four cholesterol-contained diets (0.8, 1.6, 2.4 and 3.2%) and a control diet for eight weeks. All fish-fed cholesterol diets showed increased body weight, but accumulated cholesterol (the peak level was in the 1.6% cholesterol group). Then, we selected 1.6% cholesterol and control diets for further analysis. The high cholesterol diet impaired liver function and reduced mitochondria number in fish. Furthermore, high cholesterol intake triggered protective adaptation via (1) inhibiting endogenous cholesterol synthesis, (2) elevating the expression of genes related to cholesterol esterification and efflux, and (3) promoting chenodeoxycholic acid synthesis and efflux. Accordingly, high cholesterol intake reshaped the fish gut microbiome by increasing the abundance of Lactobacillus spp. and Mycobacterium spp., both of which are involved in cholesterol and/or bile acids catabolism. Moreover, high cholesterol intake inhibited lipid catabolic activities through mitochondrial β-oxidation, and lysosome-mediated lipophagy, and depressed insulin signaling sensitivity. Protein catabolism was elevated as a compulsory response to maintain energy homeostasis. Therefore, although high cholesterol intake promoted growth, it led to metabolic disorders in fish. For the first time, this study provides evidence for the systemic metabolic response to high cholesterol intake in fish. This knowledge contributes to an understanding of the metabolic syndromes caused by high cholesterol intake or deposition in fish. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42995-022-00158-7.
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Targeting maternal gut microbiome to improve mental health outcomes-a pilot feasibility trial.
BACKGROUND: Perinatal depression and anxiety (PDA) is prevalent in new and expectant mothers, affecting millions of women worldwide. Those with a history of mood and anxiety disorders are at the greatest risk of experiencing PDA in a subsequent pregnancy. Current safety concerns with pharmacological treatments have led to a greater need for adjunctive treatment options for PDA. Changes in the composition of the microbiome have been associated with various diseases during pregnancy, and these changes are thought to play some role in perinatal mood disorders. While the relationship between PDA and the microbiome has not been explored, evidence suggests that nutritional interventions with fiber, fish oils, and probiotics may play a favorable role in neuropsychiatric outcomes during and after pregnancy. The primary objective of the present study is to assess the feasibility and acceptability of a combination of nonpharmacological interventions to maintain stability in pregnant women who have a history of depression and/or anxiety. This study will also aim to understand ease of recruitment and protocol adherence in this cohort. METHODS: This is a single-centered, partially randomized, placebo-controlled, double-blind feasibility trial. One hundred pregnant women with a history of depression and/or anxiety/PDA will be recruited and randomized into one of four arms, which could include the following: receiving a daily dose of both investigational products and dietary counseling on increasing dietary fiber, receiving a daily dose of both investigational drugs only, receiving fish oil investigational product and placebo, and a control arm with no intervention. The study involves six study visits, all of which can be conducted virtually every 3 months from the time of enrollment. At all study visits, information on diet, mental health, physical activity, and sleep quality will be collected. Additionally, all participants will provide a stool sample at each visit. DISCUSSION: It is anticipated that pregnant women with a history of depression and anxiety will be particularly interested in partaking in this trial, resulting in favorable recruitment rates. Given the positive findings of omega-3 fatty acids (O3FAs) and probiotic supplements on mental health symptoms in nonpregnant adults, we expect a similar trend in PDA symptoms, with a low likelihood of adverse events. This study will build the foundation for larger powered studies to further contribute evidence for the efficacy of this potential preventative treatment option. TRIAL REGISTRATION: This trial was registered at ClinicalTrials/gov on October 6, 2023; NCT06074250. Trial Sponsor: The Canadian College of Naturopathic Medicine, 1255 Sheppard Ave E, Toronto, ON M2K 1E2, 416-498-1255.
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Stress-Resilience Impacts Psychological Wellbeing: Evidence from Brain-Gut Microbiome Interactions.
The brain-gut-microbiome (BGM) system plays an influential role on mental health. We characterized BGM patterns related to resilience using fecal samples and multimodal MRI. Data integration analysis using latent components showed the high resilience phenotype was associated with lower depression and anxiety symptoms, higher frequency of bacterial transcriptomes (related to environmental adaptation, genetic propagation, energy metabolism, anti-inflammation), increased metabolites (N-acetylglutamate; dimethylglycine), and cortical signatures (increased resting state functional connectivity between reward circuits and sensorimotor networks; decreased grey matter volume and white matter tracts within the emotion regulation network). Our findings support a multi-omic signature involving the BGM system suggesting that resilience impacts psychological symptoms, emotion regulation and cognitive function as reflected by unique neural correlates and microbiome function supporting eubiosis and gut barrier integrity. Bacterial transcriptomes provided the highest classification accuracy suggesting that the microbiome is critical in shaping resilience and highlights that microbiome modifications can optimize mental health.
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Gut Microbiome-Driven Microglial Activation Links Dysbiosis to Pain in Interstitial Cystitis/Bladder Pain Syndrome.
BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain associated with urinary frequency and comorbid anxiety and depression. Recent studies in IC/BPS patients and rodent models implicate fecal dysbiosis and increased systemic exposure to endotoxin. These changes potentially elicit innate immune responses via the activation of microglial cells in the central nervous system, key mediators of pain. Microglial ablation and inactivation have previously been associated with analgesia in preclinical studies, underscoring the role of microglia in IC/BPS pain. Here, we investigated whether IC/BPS-associated fecal microbiota differentially activate microglia and whether activation correlates with patient symptoms. METHODS: Microbiome-microglia interactions were assessed using three complementary in vitro culture models: BV2 cells, enriched primary microglia (~ 95% microglia), and mixed glial cultures (microglia and astrocytes). Microglial cultures were exposed to heat-killed, stool-derived microbiota, and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), RANTES/CCL5, and interleukin-6 (IL-6) were quantified by ELISA. Cytokine levels were evaluated for patients and controls and correlated with patient-reported genitourinary pain index (GUPI) scores. RESULTS: In all culture models, microglia exhibited significantly increased proinflammatory responses to fecal microbiota of IC/BPS patients relative to controls. Mixed glial cultures, incorporating astrocyte-microglia interactions, exhibited the most robust cytokine responses. Cytokine levels positively correlated with GUPI pain scores. CONCLUSIONS: Together, these findings further support a role for gut dysbiosis in IC/BPS symptoms and suggest microglial activation and glial-glial interactions as a contributing mechanism. Understanding gut-brain axis interactions in IC/BPS will thus enable development of novel microbiome-based therapies for treating IC/BPS patients.
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The microbiota-gut-brain axis perspective: mechanisms and intervention strategies for the comorbidity of chronic constipation and depression.
BACKGROUND: Chronic constipation and depression are highly prevalent worldwide. These two conditions frequently co-occur in clinical practice. Accumulating evidence indicates that gut microbiota dysbiosis mediates this comorbidity through the microbiota-gut-brain axis (MGBA). METHODS: This narrative review systematically summarizes current research on MGBA bidirectional communication mechanisms, gut microbiota alterations in comorbid patients, and microbiota-targeted intervention strategies. RESULTS: The MGBA facilitates bidirectional communication through four major pathways: neural pathways via the vagus nerve, immune pathways via cytokines, endocrine pathways via the HPA axis, and metabolic pathways via short-chain fatty acids and neurotransmitter precursors. Gut dysbiosis is associated with comorbidity and may contribute to its pathogenesis through multiple mechanisms. First, neurotransmitter metabolism becomes dysregulated, particularly in the serotonin and GABA systems. Second, chronic low-grade inflammation develops with elevated pro-inflammatory cytokines. Third, intestinal barrier dysfunction occurs, leading to increased permeability and bacterial translocation. Fourth, HPA axis hyperactivity emerges. Fifth, production of microbial metabolites is altered, including short-chain fatty acids and tryptophan metabolites. Comorbid patients exhibit characteristic microbiota signatures. These include reduced abundance of butyrate-producing bacteria such as Faecalibacterium, Roseburia, and Coprococcus. Microbial diversity decreases significantly. Pro-inflammatory taxa become enriched. Several evidence-based interventions show promise. These include psychobiotics, fecal microbiota transplantation, and dietary modifications such as Mediterranean diet and high-fiber intake. Exercise and integrative approaches including traditional Chinese medicine also demonstrate beneficial effects. CONCLUSION: The gut microbiota represents a critical hub connecting gastrointestinal and mental health. Microbiota-targeted therapies offer promising strategies for managing chronic constipation-depression comorbidity. Future research should establish causal relationships and develop reliable microbial biomarkers. Precision medicine approaches based on individual microbiome profiles are needed to optimize therapeutic outcomes.
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Therapeutic Effects of Baicalin on Diseases Related to Gut-Brain Axis Dysfunctions.
The gut-brain axis is an active area of research. Several representative diseases, including central nervous system disorders (Alzheimer's disease, Parkinson's disease, and depression), metabolic disorders (obesity-related diseases), and intestinal disorders (inflammatory bowel disease and dysbiosis), are associated with the dysfunctional gut-brain axis. Baicalin, a bioactive flavonoid extracted from Scutellaria baicalensis, is reported to exert various pharmacological effects. This narrative review summarizes the molecular mechanisms and potential targets of baicalin in disorders of the gut-brain axis. Baicalin protects the central nervous system through anti-neuroinflammatory and anti-neuronal apoptotic effects, suppresses obesity through anti-inflammatory and antioxidant effects, and alleviates intestinal disorders through regulatory effects on intestinal microorganisms and short-chain fatty acid production. The bioactivities of baicalin are mediated through the gut-brain axis. This review comprehensively summarizes the regulatory role of baicalin in gut-brain axis disorders, laying a foundation for future research, although further confirmatory basic research is required.
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A personalized diet intervention improves depression symptoms and changes microbiota and metabolite profiles among community-dwelling older adults.
INTRODUCTION: The impact of diet on mental well-being and gut microorganisms in humans is well recognized. However, research on the connections between food nutrients, gut microbiota, and mental health remains limited. To address this, the present study aimed to assess the effects of a personalized diet, based on individual needs and aligned with the Mediterranean diet principles, on depression symptoms, quality of life, nutritional intake, and gut microbiota changes among older adults living in the community. METHODS: The intervention involved regular visits from a registered dietitian, who provided tailored dietary recommendations. During the 6-month study, participants completed questionnaires to evaluate their depression levels, quality of life, and dietary habits. Additionally, they provided stool samples for analysis of gut microbiota and metabolites. RESULTS: The results demonstrated that the personalized dietary intervention reduced depression symptoms and improved the quality of life among older adults. Furthermore, significant changes in the intake of certain nutrients, such as folate, lutein, zeaxanthin, EPA, and DHA, were observed following the intervention. Moreover, the intervention was associated with increased diversity in the gut microbiome and reduced total short-chain fatty acids, the main metabolites produced by gut microorganisms. The study also revealed correlations between food nutrients, gut microbiota, and mental health parameters. DISCUSSION: In conclusion, this research highlights the potential advantages of personalized dietary interventions in managing depression and enhancing overall well-being among older populations. It also sheds light on the role of gut microbiota and its metabolites in these effects. The findings offer valuable insights into the significance of nutrition and gut health for mental well-being in older adults.