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Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: A randomized clinical trial.
BACKGROUND: Disturbance in the equilibrium of the gut microbiota has been involved in the pathophysiology of depression. Probiotics have the potential to healthfully modulate the gut microbiome. Prebiotics could also be effective by stimulation of growth of some bacterial species in the gut microbiota. OBJECTIVE: The aim of this double blind clinical trial, was to compare the effect of supplementation with the probiotic and prebiotic on the Beck Depression Inventory (BDI) score as a primary outcome as well as the kynurenine/tryptophan ratio and tryptophan/branch chain amino acids (BCAAs) ratio as secondary outcomes in patients with major depressive disorder (MDD). DESIGN: One hundred and ten depressed patients were randomly assigned to receive the probiotic (Lactobacillus helveticus and Bifidobacterium longum), prebiotic (galactooligosaccharide) or placebo for 8 weeks. Serum tryptophan and BCAAs were measured by HPLC, and kynurenine by ELISA kit. Dietary intake and physical activity of the participants were recorded at baseline. RESULTS: A total of 81 subjects (aged 36.5 ± 8.03 y; mean (95% CI), 2.27 (1.76-2.93) y of depression duration) completed the trial (28 in the probiotic group, 27 in the prebiotic group, and 26 in the placebo group). From baseline to 8 weeks, probiotic supplementation resulted in a significant decrease in BDI score (17.39-9.1) compared to the placebo (18.18-15.55) and prebiotic (19.72-14.14) supplementation (p = 0.042). Inter-group comparison indicated no significant differences among the groups in terms of serum kynurenine/tryptophan ratio and tryptophan/BCAAs ratio. However, the kynurenine/tryptophan ratio decreased significantly in the probiotic group compared to the placebo group after adjusting for serum isoleucine (p = 0.048). In addition, the tryptophan/isoleucine ratio increased significantly in the probiotic group when compared to the placebo group (p = 0.023). CONCLUSION: Overall, 8 weeks of probiotic supplements to subjects with MDD resulted in an improvement in BDI score compared with placebo whereas no significant effect of prebiotic supplementation was seen. Study was registered in IRCT.ir under IRCT2015092924271N1.
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The Role of Various Types of Diets in the Treatments of Depressive Disorders.
Depression is a prevalent and disabling psychiatric disorder, characterized by persistent disturbances in mood, cognition, and physiological processes, which collectively lead to substantial impairments in daily functioning and quality of life. This review provides a comprehensive overview of the biological mechanisms implicated in the pathophysiology of depression, including neurotransmitter dysregulation, oxidative stress, inflammatory processes, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, mitochondrial impairment, and alterations in the gut-brain axis. Furthermore, it explores the role of diet in both the prevention and management of depression, with particular emphasis on Mediterranean, anti-inflammatory, and ketogenic dietary patterns, while contrasting these with the detrimental impact of a Western dietary pattern. Specific nutrients-such as n-3 polyunsaturated fatty acids (PUFAs), B-complex vitamins, vitamins D and E, zinc, selenium, and polyphenols-are highlighted for their potential roles in modulating neurotransmission, attenuating inflammation, and supporting gut microbiota homeostasis. Despite growing scientific interest in nutrition-based interventions, current evidence on the comparative efficacy of different dietary approaches remains limited. Future research is warranted to elucidate the therapeutic potential of dietary strategies as adjuncts to conventional treatments for depression and to facilitate the development of evidence-based nutritional recommendations for clinical practice.
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Alteration of the intestinal microbiota and serum metabolites in a mouse model of Pon1 gene ablation.
Mutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.
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Maternal SSRI Use During Pregnancy: Links Between Gut Microbiome, Offspring Behaviour, and Brain Transcriptomics.
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to treat maternal depression during pregnancy, yet their potential impact on foetal brain development remains a concern. Although maternal illness is a known confounder, growing evidence from both clinical and preclinical studies suggests that perinatal SSRI exposure may independently influence neurodevelopmental outcomes. This review draws on rodent studies to explore how developmental SSRI exposure affects the gut microbiome, maternal behaviour, myelination, and offspring social behaviour. Elevated serotonin levels caused by SSRIs can alter both brain development and the maternal gut microbiota, with possible long-term effects on offspring. Behaviourally, SSRI-exposed offspring often show reduced social play, altered social interactions, and sex-specific effects on aggression and sexual behaviour, in which males appear more sensitive to these effects than females. Maternal care is only modestly affected. Overall, developmental SSRI exposure in the absence of maternal illness can disrupt brain development and social behaviour in offspring, potentially through gut-brain axis mechanisms and altered myelination.
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[«Brain-gut-microbiome» axis in patients with Parkinson's disease].
Parkinson's disease (PD) is one of the most common motor neurological diseases. The clinical presentation of PD includes both motor symptoms (hypokinesia, muscle rigidity, and tremor) and non-motor manifestations (asthenia, depression, hyposmia), as well as cognitive disorders. The primary link in PD pathogenesis is considered to be the accumulation of pathological α-synuclein; however, neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the Brain-gut microbiome axis also contribute to the pathological processes. This review of modern medical literature, encompassing domestic and foreign authors, summarizes recent studies on the significance of gastrointestinal tract changes in PD patients. The analysis revealed the involvement of the microbiome and specific bacterial taxonomic groups in the development of PD. In addition, the accumulation of α-synuclein, according to recent data, begins specifically in the nerve plexuses of the intestine and then spreads along the nerves upward into the central nervous system, affecting the substantia nigra, in particular.
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Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls.
OBJECTIVES: Anorexia nervosa (AN) is a heterogeneous eating disorder associated with alterations of body structure and the gut microbiome. We aimed to investigate the gut microbiota composition of a large female cohort including different BMI groups and activity levels along with body composition parameters. METHOD: 106 female participants were included in this cross-sectional study: AN patients (n = 18), athletes (n = 20), normal weight (n = 26), overweight (n = 22), and obese women (n = 20). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. The software Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Additionally, we performed anthropometric assessments, ultrasound measurements of subcutaneous adipose tissue thickness, bioimpedance analysis, administered depression inventories, and ascertained laboratory parameters and dietary intakes. RESULTS: Alpha diversity was particularly lower in AN patients and obese participants compared to other groups, while athletes showed highest alpha diversity. Several categories significantly associated with community structure were identified: body fat parameters, serum lipids, CRP, depression scales and smoking. Comparative analysis revealed Coriobacteriaceae as the only enriched phylotype in AN compared to other entities (LDA score >3.5). DISCUSSION: This study provides further evidence of intestinal dysbiosis in AN and sheds light on characteristics of the gut microbiome in different BMI and physical activity groups. These insights point to new modulation possibilities of the gut microbiota which could improve the standard therapy of AN.
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Pathoetiology and pathophysiology of borderline personality: Role of prenatal factors, gut microbiome, mu- and kappa-opioid receptors in amygdala-PFC interactions.
The pathoetiology and pathophysiology of borderline personality disorder (BPD) have been relatively under-explored. Consequently, no targetted pharmaceutical treatments or preventative interventions are available. The current article reviews the available data on the biological underpinnings of BPD, highlighting a role for early developmental processes, including prenatal stress and maternal dysbiosis, in BPD pathoetiology. Such factors are proposed to drive alterations in the infant's gut microbiome, in turn modulating amygdala development and the amygdala's two-way interactions with other brain regions. Alterations in opioidergic activity, including variations in the ratio of the mu-and kappa-opioid receptors seem a significant aspect of BPD pathophysiology, contributing to its comorbidities with depression, anxiety, impulsivity and addiction. Stress and dysphoria are commonly experienced in people classed with BPD. A growing body of data, across a host of medical conditions, indicate that stress and mood dysregulation may be intimately associated with gut dysbiosis and increased gut permeability, coupled to heightened levels of oxidative stress and immune-inflammatory activity. It urgently requires investigation as to the relevance of such gut changes in the course of BPD symptomatology. Accumulating data indicates that BPD symptom exacerbations may be linked to cyclical variations in estrogen, in turn decreasing serotonin and local melatonin synthesis, and thereby overlapping with the pathophysiology of migraine and endometriosis, which also have a heightened association with BPD. Future research directions and treatment implications are indicated.
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Consumption of Butylated Starch Alleviates the Chronic Restraint Stress-Induced Neurobehavioral and Gut Barrier Deficits Through Reshaping the Gut Microbiota.
The beneficial effect of short-chain fatty acids (SCFAs) on host health has been well recognized based on the booming knowledge from gut microbiome research. The role of SCFA in influencing psychological function is highlighted in recent years but has not been fully elucidated. In this study, the SCFA-acylated starches were used to accomplish a sizeable intestine-targeted release of the SCFAs, and the neurobehavioral, immunological, and microbial effects were further investigated. Acetylated-, butylated-, and isobutylated-starch could attenuate the depression-like behaviors and excessive corticosterone production in chronically stressed mice. Butylated- starch significantly reduced the colonic permeability via increasing the tight junction proteins (including ZO-1, Claudin, and Occludin) gene expression and reduced the level of the inflammatory cytokines (including IL-1β and IL-6). The butylated starch's neurological and immunological benefits may be derived from the gut microbiome modifications, including normalizing the abundance of certain beneficial microbes (Odoribacter and Oscillibacter) and metabolomic pathways (Tryptophan synthesis and Inositol degradation). The present findings further validate the brain-beneficial effect of butyrate and offer novel guidance for developing novel food or dietary supplements for improving mental health.
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From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.
The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.
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Gut microbiota is associated with weight gain in children treated with atypical antipsychotic: A pilot longitudinal study.
We studied longitudinal changes in the microbiome with weight gain during atypical antipsychotics (APs) treatment. 43 inpatients naive to AP paediatric medication were included in the longitudinal microbiota study. The baseline composition of the gut microbiome in the case group was characterised by an increase in Parabacteroides and Eubacterium_hallii_group. During the follow-up, the relative abundances of Romboutsia and Klebsiella increased significantly after 3 months of AP treatment; however, no significant changes in these two gut bacteria were observed in the control group. The baseline composition of the gut microbiome contributed to the risk of AP-associated weight gain.