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A Narrative Review on the Role of Microbiota and Microglia in Premotor Symptoms of Parkinson's Disease.
With the advent of medical technology and the sustenance of a longer lifespan, an increase in the number of age-related neurodegenerative diseases, including Parkinson's disease (PD), is inevitable. Although current treatments for PD provide remarkable symptomatic relief for a few years, their side effects, combined with the progression in neurodegeneration, pose an urgent challenge for development of more effective treatments for this devastating disease. The challenge is further exacerbated by the unknown etiology in most PD cases. Nonetheless, progress in early identification of the premorbid/prodromal symptoms as well as understanding processes leading to their manifestation may help provide novel preventive and/or intervention strategies. The triad of the best-characterized and inter-related symptoms of prodromal PD include hyposmia (decrease sense of smell), constipation, and major depressive disorder (MDD). Recent revelations indicate a crucial role for the gut microbiota (GM) not only in maintaining the integrity of the gastrointestinal system but also that of the central nervous system via its bidirectional relationship with the brain, commonly referred to as the gut-brain-axis (GBA). Moreover, neuroinflammation, underscored by microglial activation, is believed to play a critical role in neurodegenerative as well as neuropsychiatric disorders including MDD. Here, we delve into the primary roles of GM/GBA and microglia, as well as their interactions, with the aim of providing novel diagnostic and/or treatments in PD. Regarding the treatments, we mention potential use of pre- post- or pro-biotics, and nicotinic or toll-like receptor modulators.
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The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System-A Systematic Review.
Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut-brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut-brain axis based on selected diseases, i.e., Alzheimer's disease, Parkinson's disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut-brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota-gut-brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome.
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Gut microbiota and health.
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Exploring the role of diet in modulating stress and emotional health: a review on mental nutrition and cognitive resilience.
The rise in mental-health-related disorders, including anxiety, depression, and cognitive impairment worldwide, has increased the demand for preventative non-pharmacological interventions and intervention aimed at modifiable lifestyle factors - particularly diet. Growing evidence shows that plant-based nutrition, with its anti-inflammatory and neuroprotective effects, is critically important for cognitive resilience, emotional stability, and mental wellbeing. Essential nutrient and bioactive compounds such as ω-3 fatty acids, polyphenols, B vitamins, magnesium, and probiotics themselves act on the gut-brain axis to alleviate neuroinflammatory stress. Functional and adaptogenic foods - for example, Ashwagandha, Rhodiola, and Holy Basil - are becoming the focus of interest as they play a significant role in cortisol control and stress adaptation. All plant-based dietary patterns, such as the Mediterranean, DASH (Dietary Approaches to Stop Hypertension), and plant-based diets, show comparable associations with lower risk for depression, anxiety, and cognitive deficits through enhancing gut microbiome richness and balancing neurotransmitters. This review outlines the scientific basis of mental nutrition, highlighting the interconnections between dietary patterns, gut microbiota composition, diet-mediated modulation of neurotransmitter levels, and neuroinflammatory pathways that collectively influence mental health. © 2026 Society of Chemical Industry.
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Multi-omics data reveals the disturbance of glycerophospholipid metabolism caused by disordered gut microbiota in depressed mice.
INTRODUCTION: Although researchers have done intensive research on depression, its pathogenesis is still not fully explained. More and more evidence suggests that gut microbiota is closely related to the onset of depression; but its specific functional ways are not clearly identified. OBJECTIVES: The purpose of our work was to find out how the gut microbiota was involved in the onset of depression, and to identify the potential ways to link the gut and brain in mice with depressive-like behaviors (DLB). METHODS: We used the chronic restraint stress (CRS)-induced depression model here. Gut microbiota compositions in fecal samples, lipid metabolism (in fecal, serum and hippocampus samples) and neurotransmitters in hippocampus samples were detected. RESULTS: We found that the 7 of 13 differential genera that significantly correlated with DLB belonged to phylum Firmicutes. The differential lipid metabolites in fecal samples mainly belonged to glycerophospholipids (GP) and fatty acids (FA) metabolism, and three important "metabolite type-bacterial taxa" correlated pairs were identified: "FA/GP-Firmicutes", "FA/GP-Akkermansia", and "FA/GP-Bifidobacterium". The key differential lipid metabolites significantly correlated with DLB mainly belonged to FA and GP, and the DLB-related metagenomic genes were consistently enriched in GP metabolism and FA metabolism. Three significantly changed short-chain fatty acids (SCFAs) were significantly correlated with the majority of differential genera. Meanwhile, we found that the differential lipid metabolites in serum and hippocampus samples were mainly mapped into the GP metabolism, and there were four differential neurotransmitters from the tryptophan pathway in hippocampus samples. CONCLUSION: Together, our findings could provide novel insights into the role of "microbiota-gut-brain" (MGB) axis in depression, and indicate that the gut microbiota might have a vital role in the onset of DLB by affecting the peripheral/central GP metabolism and tryptophan pathway. The "Firmicutes-SCFAs-GP metabolism-Tryptophan pathway" might be a possible way to link the gut and brain in depressed mice.
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The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.
The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.
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Gut Microbiome Composition and Variance Are Modified by Degree of Growth Failure in Preterm Infants: A Prospective Study.
Background/Objectives: Preterm infants often require increased caloric intake to maintain appropriate growth while in the neonatal intensive care unit (NICU). Emerging evidence suggests that alterations of the gut microbiome may play a role in infant and childhood growth patterns. The fecal microbiome patterns in infants with normal and poor growth patterns were classified in this study. Methods: We conducted a prospective trial of infants of less than 29 weeks' gestation with an embedded case-control analysis of infants with normal or poor growth patterns. Fecal samples were collected weekly from infants on full enteral feeds and analyzed blindly using 16s rRNA next-generation sequencing. The relationship between gut microbial diversity and composition and growth pattern and trajectory were assessed. Results: A total of 115 infants were enrolled in the trial with 263 fecal samples selected from 87 enrolled infants for analysis. In total, 37 samples were available from the normal growth cohort, 56 samples from the poor growth cohort, and 170 samples were available for analysis from the very poor growth cohort. Analysis of relative abundance revealed increased representation of Veillonella, Bifidobacterium, and Clostridium in very poor growth infants compared to normal growth infants. Variation in specific taxa was also found to vary significantly across post-menstrual age depending on the degree of growth failure. Conclusions: Gut microbiome composition and variance was modified by the degree of growth failure in our cohort of preterm infants. Our study adds to the growing body of evidence that alteration of the microbiome is associated with poor growth in preterm infants. This may ultimately represent a therapeutic target for growth failure in preterm infants.
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Microbiota-mediated effects of Parkinson's disease medications on Parkinsonian non-motor symptoms in male transgenic mice.
Parkinson's disease (PD) is characterized by motor symptoms and a loss of dopaminergic neurons, as well as a variety of non-motor symptoms, including constipation, depression, and anxiety. Recently, evidence has also accumulated for a link between gut microbiota and PD. Most PD patients are on dopamine replacement therapy, primarily a combination of L-DOPA and carbidopa; however, the effect of these medications on the microbiota and non-motor symptoms in PD is still unclear. In this study, we explored the effects of chronic oral treatment with L-DOPA plus carbidopa (LDCD) on the gut microbiota and non-motor symptoms in males of a transgenic mouse model of PD (dbl-PAC-Tg(SNCAA53T);Snca-/-). To further test whether the effects of these PD medications were mediated by the gut microbiota, oral antibiotic treatment (Abx; vancomycin and neomycin) was included both with and without concurrent LDCD treatment. Post-treatment, the gastrointestinal, motor, and behavioral phenotypes were profiled, and fecal, ileal, and jejunal samples were analyzed for gut microbiota composition by 16S sequencing. LDCD treatment was found to improve symptoms of constipation and depression in this model, concurrent with increases in Turicibacter abundance in the ileum. Abx treatment worsened the symptoms of constipation, possibly through decreased levels of short-chain fatty acids and disrupted gut barrier function. LDCD + Abx treatment showed an interaction effect on behavioral symptoms that was also associated with ileal Turicibacter levels. This study demonstrates that, in a mouse model, PD medications and antibiotics affect PD-related non-motor symptoms potentially via the gut microbiota.IMPORTANCEThe motor symptoms of Parkinson's disease (PD) are caused by a loss of dopamine-producing neurons and are commonly treated with dopamine replacement therapy (L-DOPA plus carbidopa). PD has also been associated with altered gut microbiota composition. However, the effects of these PD medications on PD-related non-motor symptoms and the gut microbiota have not been well characterized. This study uses a transgenic mouse model of PD to help resolve medication-induced microbiota alterations from those that are potentially disease relevant within a PD context, and explores how long-term treatment may interact with the gut microbiota to impact non-motor symptoms.
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Gut emotions - mechanisms of action of probiotics as novel therapeutic targets for depression and anxiety disorders.
A priority clinical and research agenda in mood and anxiety disorders is to identify determinants that influence illness trajectory and outcome. Over the past decade, studies have demonstrated a bidirectional relationship between the gut microbiome and brain function (i.e., the microbiota-gut-brain axis). Probiotic treatments and developmental analysis of the microbiome may provide potential treatments and preventative measures for depressive and anxiety disorders. This systematic literature review aims to identify original studies linking the gut microbiota to major depressive disorder and anxiety disorders. Furthermore, this review searched for original reports focusing on possible therapeutic and preventative effects of probiotics for these debilitating conditions. Accumulating data indicate that the gut microbiota communicates with the CNS through neural, endocrine and immune pathways. Studies in germ-free animals indicate that the microbiota is involved in the regulation of the stress response (e.g., hypothalamic-pituitary-adrenal axis) and in CNS development at critical stages. Probiotics attenuate anxiety and depressive-like behaviors in experimental animal models. Notwithstanding some inconsistencies and methodological limitations across trials, clinical studies suggest that probiotics may mitigate anxiety symptoms. However, future studies should investigate the anxiolytic and antidepressant effects of probiotics in more phenotypically homogeneous populations. In conclusion, the emerging concept of a gut microbiota-brain axis suggests that the modulation of the gut microbiota may provide a novel therapeutic target for the treatment and/or prevention of mood and anxiety disorders.
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Ketogenic diet for mood disorders from animal models to clinical application.
Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD) are often resistant to current pharmacological treatment. Therefore, various alternative therapeutic approaches including diets are, therefore, under investigation. Ketogenic diet (KD) is effective for treatment-resistant epilepsy and metabolic diseases, however, only a few clinical studies suggest its beneficial effect also for mental disorders. Animal models are a useful tool to uncover the underlying mechanisms of therapeutic effects. Women have a twice-higher prevalence of mood disorders but very little is known about sex differences in nutritional psychiatry. In this review, we aim to summarize current knowledge of the sex-specific effects of KD in mood disorders. Ketone bodies improve mitochondrial functions and suppress oxidative stress, inducing neuroprotective and anti-inflammatory effects which are both beneficial for mental health. Limited data also suggest KD-induced improvement of monoaminergic circuits and hypothalamus-pituitary-adrenal axis-the key pathophysiological pathways of mood disorders. Gut microbiome is an important mediator of the beneficial and detrimental effects of diet on brain functioning and mental health. Gut microbiota composition is affected in mood disorders but its role in the therapeutic effects of different diets, including KD, remains poorly understood. Still little is known about sex differences in the effects of KD on mental health as well as on metabolism and body weight. Some animal studies used both sexes but did not find differences in behavior, body weight loss or gut microbiota composition. More studies, both on a preclinical and clinical level, are needed to better understand sex-specific effects of KD on mental health.