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Understanding the Impact of the Gut Microbiome on Mental Health: A Systematic Review.
Mental health is a serious issue, with mental health disorders affecting millions of people globally. Gut microbiota has received considerable attention because of its potential role in the pathogenesis of mental health disorders. This systematic review synthesized 15 studies exploring the effects of the gut microbiome on depression, anxiety, schizophrenia, and bipolar disorder, with qualitative and quantitative insights. The studies were conducted in different countries and employed various methods including 16S rRNA sequencing and metagenomic analysis with sample sizes varying from 50 to 600. Some of the key findings were that depression was associated with reduced microbial diversity and high levels of Firmicutes, and anxiety was associated with low levels of short-chain fatty acid (SCFA)-producing bacteria and high levels of Proteobacteria. Schizophrenia was related to endotoxemia and a reduction in the Lactobacillus count whereas bipolar disorder displayed a shift in the Firmicutes/Bacteroidetes ratio. Of interest, probiotics and dietary changes were as effective as drug treatment leading to symptom alleviation in many patients. It was found that depression was linked to less diverse gut bacteria while anxiety was associated with an increase in inflammatory bacteria. People with bipolar disorder were also found to have different gut bacteria patterns. This review also emphasizes the importance of the gut microbiota in the pathophysiology of mental disorders and the promising value of targeting microbiomes in pharmacological treatment approaches.
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Substance-Induced Psychiatric Disorders, Epigenetic and Microbiome Alterations, and Potential for Therapeutic Interventions.
Substance use disorders (SUDs) are complex biopsychosocial diseases that cause neurocognitive deficits and neurological impairments by altering the gene expression in reward-related brain areas. Repeated drug use gives rise to alterations in DNA methylation, histone modifications, and the expression of microRNAs in several brain areas that may be associated with the development of psychotic symptoms. The first section of this review discusses how substance use contributes to the development of psychotic symptoms via epigenetic alterations. Then, we present more evidence about the link between SUDs and brain epigenetic alterations. The next section presents associations between paternal and maternal exposure to substances and epigenetic alterations in the brains of offspring and the role of maternal diet in preventing substance-induced neurological impairments. Then, we introduce potential therapeutic agents/approaches such as methyl-rich diets to modify epigenetic alterations for alleviating psychotic symptoms or depression in SUDs. Next, we discuss how substance use-gut microbiome interactions contribute to the development of neurological impairments through epigenetic alterations and how gut microbiome-derived metabolites may become new therapeutics for normalizing epigenetic aberrations. Finally, we address possible challenges and future perspectives for alleviating psychotic symptoms and depression in patients with SUDs by modulating diets, the epigenome, and gut microbiome.
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Implications of gut microbiota dysbiosis and fecal metabolite changes in psychologically stressed mice.
INTRODUCTION: Psychological stress can induce affective disorders. Gut microbiota plays a vital role in emotional function regulation; however, the association between gut microbiota and psychological stress is poorly understood. We investigated effects of psychological stress on the gut microbiome and fecal metabolites and assessed the relationship between affective disorder behavior and altered fecal microbiota. METHODS: A psychological stress model was established in C57BL/6J mice using a communication box. Sucrose preference test, forced swim test, and open field test helped assess anxiety- and depression-like behaviors. Fecal microbiota transplantation (FMT) was conducted using fecal samples from stressed and non-stressed mice. Moreover, 16S rRNA gene sequencing and untargeted metabolomics were performed. RESULTS: After stress exposure for 14 days, a significant increase in anxiety- and depression-like behaviors was observed. FMT of "affective disorder microbiota" from psychologically stressed mice increased stress sensitivity relative to FMT of "normal microbiota" from non-stressed mice. 16S rRNA gene sequencing revealed decreased abundance of Bacteroides, Alistipes, and Lactobacillus and increased abundance of Parasutterella and Rikenellaceae_RC9_gut_group in stressed mice; furthermore, stressed mice showed differential metabolite profiles. KEGG pathway analysis indicated that differential metabolites were chiefly involved in the downregulated pathways of α-linolenic acid metabolism, taste transduction, and galactose metabolism. Alistipes and Bacteroides were mainly positively correlated and Parasutterella was mainly negatively correlated with diverse metabolites. DISCUSSION: Our findings suggest that gut microbiome dysbiosis contributes to affective disorder development in response to psychological stress.
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Characterization of the gut microbiota among Veterans with unique military-related exposures and high prevalence of chronic health conditions: A United States-Veteran Microbiome Project (US-VMP) study.
The gut microbiome is impacted by environmental exposures and has been implicated in many physical and mental health conditions, including anxiety disorders, affective disorders, and trauma- and stressor-related disorders such as posttraumatic stress disorder (PTSD). United States (US) military Veterans are a unique population in that their military-related exposures can have consequences for both physical and mental health, but the gut microbiome of this population has been understudied. In this publication, we describe exposures, health conditions, and medication use of Veterans in the US Veteran Microbiome Project (US-VMP) and examine the associations between these characteristics and the gut microbiota. This cohort included 331 US Veterans seeking healthcare with the Veterans Health Administration who were 83% male with an average (±SD) age of 47.6 ± 13.4 years. The cohort displayed a high prevalence of PTSD (49.8%) and history of traumatic brain injuries (76.1%), and high current use of prescription medications (74.9%) to treat various acute and chronic conditions. We observed significant associations between the gut microbiota composition and gastroenteritis, peripheral vascular disease (PVD), bipolar disorders, symptoms of severe depression based on the Beck Depression Inventory, stimulant and opioid use disorders, beta-blockers, serotonin and norepinephrine reuptake inhibitor antidepressants, diabetes medications, and proton pump inhibitors. Many of the Veteran characteristics examined were associated with altered relative abundances of specific taxa. We found that PVD and cardiovascular disease were associated with lower microbiota diversity in the gut (i.e., α-diversity), while supplemental vitamin use was associated with higher α-diversity. Our study contributes novel insights as to whether the unique exposures of Veterans in this cohort correlate with gut microbiota characteristics and, in line with previous findings with other population-level studies of the microbiome, confirms associations between numerous health conditions and medications with the gut microbiome.
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Microbiota and Alcohol Use Disorder: Are Psychobiotics a Novel Therapeutic Strategy?
In recent years, there has been an exciting focus of research attempting to understand neuropsychiatric disorders from a holistic perspective in order to determine the role of gut microbiota in the aetiology and pathogenesis of such disorders. Thus, the possible therapeutic benefits of targeting gut microbiota are being explored for conditions such as stress, depression or schizophrenia. Growing evidence indicates that there is bidirectional communication between gut microbiota and the brain that has an effect on normal CNS functioning and behavioural responses. Alcohol abuse damages the gastrointestinal tract, alters gut microbiota and induces neuroinflammation and cognitive decline. The relationship between alcohol abuse and hypothalamic-pituitary-adrenal axis activation, inflammation and immune regulation has been well documented. In this review, we explore the connection between microbiota, brain function and behaviour, as well as the mechanisms through which alcohol induces microbiota dysbiosis and intestinal barrier dysfunction. Finally, we propose the study of psychobiotics as a novel pharmaceutical strategy to treat alcohol use disorders.
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The neurobiology of adaptation to seasons: Relevance and correlations in bipolar disorders.
Bipolar disorders (BDs) are severe and common psychiatric disorders. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. In addition, infradian fluctuations of mood, social activity, weight and sleep patterns are very frequent in BD. Disease course with a seasonal pattern (SP) occurs in approximately 25% of depressive and 15% of manic episodes, which is coupled to a more severe disease symptomatology. The pathophysiological mechanisms of seasonal effects in BD await clarification, with likely important clinical consequences. This review aims at synthesizing available data regarding the underlying pathophysiological mechanisms of seasonality in BD patients, with implications for future research directions in the study of seasonality in BD. Three factors are suggested to play significant roles in BD with SP, namely the suprachiasmatic nuclei, as well as the melatonergic and photoperiodism systems. It is proposed that BD with SP may be considered as a complex disorder resulting from the interaction of clock gene vulnerabilities and biological clock neuroplasticity, with environmental factors, such as the response to light. Light seems to play a key role in BD with SP, mainly due to two seasonal signaling pathways: a light to cortex serotonin transporter pathway, as well as a pathway connecting light to melatonin synthesis. This provides a theoretical framework for BD with SP, including for future research and clinical management. The review proposes that future research should explore markers of seasonality in BD, such as plasma melatonin, sleep-wake rhythms (with actigraphy) and genetic or epigenetic variants within the melatonin synthesis pathway. The role of light in driving BD with SP is an active area of research. Seasonality may also be intimately linked to wider aspects of BD, including via interactions with the gut microbiome, the gut-liver axis, cholesterol regulation, aspects of metabolic syndrome, vitamin D, decreased longevity, suicide risk and medication treatment targets. Further research on the role of seasonality in BD is likely to clarify the etiology, course and treatment of BD more widely.
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Novel opportunity of treatment for psycho-cardiologic disease by gut microbiome.
Cardiovascular disease (CVD) patients combined with depression, anxiety, and other psychiatric disorders are becoming a common occurrence. There are many comorbid mechanisms, and CVD patients with psychiatric disorders have poor prognosis. Several studies have shown that dysbiosis and metabolite alterations in the gut were major risk factors for CVD and psychosomatic disorders. This review aims to summarize the mechanisms of gut microbiota and its metabolites in psycho-cardiologic disease, and the therapeutic effects of gut microbiota interventions. It is very useful to propose a new direction for the treatment of psycho-cardiologic disease.
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Gut microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients: Microbiome dysbiosis linked to COVID-19 symptoms.
COVID-19 patients often exhibit altered immune responses and neuropsychiatric symptoms during hospitalization. However, the potential interactions with gut microbiome profiles have not been fully characterized. Here, COVID-19 disease severity was classified as low (27.4%), moderate (29.8%), and critical (42.8%). Fever (66.1%) and cough (55.6%) were common symptoms. Additionally, 27.3% reported somatic symptoms, 27.3% experienced anxiety, 39% had depressive symptoms, and 80.5% reported stress. Gut microbiome profiling was performed using full-length 16S rRNA gene sequencing. Elevated interleukin-6 levels were observed in the most severe cases, indicating systemic inflammation. Reduced gut bacterial diversity was more pronounced in women and obese patients and correlated with higher disease severity. The presence of the genus Mitsuokella was significantly associated with increased physical, stress, anxiety, and depressive symptoms, and Granulicatella with critically ill patients. These findings suggest a link between mental health status, systemic inflammation, and gut dysbiosis in COVID-19 patients, emphasizing the potential of microbiome-targeted therapies to improve recovery and reduce severe complications.
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Saccharomyces boulardii improves the behaviour and emotions of spastic cerebral palsy rats through the gut-brain axis pathway.
BACKGROUND: Cerebral palsy (CP) is a kind of disability that influences motion, and children with CP also exhibit depression-like behaviour. Inflammation has been recognized as a contributor to CP and depression, and some studies suggest that the gut-brain axis may be a contributing factor. Our team observed that Saccharomyces boulardii (S. boulardii) could reduce the inflammatory level of rats with hyperbilirubinemia and improve abnormal behaviour. Both CP and depression are related to inflammation, and probiotics can improve depression by reducing inflammation. Therefore, we hypothesize that S. boulardii may improve the behaviour and emotions of spastic CP rats through the gut-brain axis pathway. METHODS: Our new rat model was produced by resecting the cortex and subcortical white matter. Seventeen-day-old CP rats were exposed to S. boulardii or vehicle control by gastric gavage for 9 days, and different behavioural domains and general conditions were tested. Inflammation was assessed by measuring the inflammatory markers IL-6 and TNF-α. Hypothalamic-pituitary-adrenal (HPA) axis activity was assessed by measuring adrenocorticotropic hormone and corticosterone in the serum. Changes in the gut microbiome were detected by 16S rRNA. RESULTS: The hemiplegic spastic CP rats we made with typical spastic paralysis exhibited depression-like behaviour. S. boulardii treatment of hemiplegic spastic CP rats improves behaviour and general conditions and significantly reduces the level of inflammation, decreases HPA axis activity, and increases gut microbiota diversity. CONCLUSIONS: The model developed in this study mimics a hemiplegic spastic cerebral palsy. Damage to the cortex and subcortical white matter of 17-day-old Sprague-Dawley (SD) rats led to spastic CP-like behaviour, and the rats exhibited symptoms of depression-like behaviour. Our results indicate that S. boulardii might have potential in treating hemiplegic spastic CP rat models or as an add-on therapy via the gut-brain axis pathway.
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From Cirrhosis to the Dysbiosis (A Loop of Cure or Complications?).
Gut dysbiosis and liver cirrhosis are two corelated complications that highly disturbs the metabolism of a normal human body. Liver cirrhosis is scarring of the hepatic tissue and gut dysbiosis is the imbalance in the microbiome of the gut. Gut dysbiosis in cirrhosis occurs due to increased permeability of the intestinal membrane which might induce immune responses and damage the normal functioning of the body. Dysbiosis can cause liver damage from cirrhosis and can further lead to liver failure by hepatocellular carcinoma. In this review we discuss if eubiosis can revert the poorly functioning cirrhotic liver to normal functioning state? A normal microbiome converts various liver products into usable forms that regulates the overgrowth of microbiome in the gut. The imbalance caused by dysbiosis retards the normal functioning of liver and increases the complications. To correct this dysbiosis, measures like use of antibiotics with probiotics and prebiotics are used. This correction of the gut microbiome serves as a ray of hope to recover from this chronic illness. In case of alcohol induced liver cirrhosis, intervention of microbes can possibly be helpful in modulating the addiction as well as associated complications like depression as microbes are known to produce and consume neurotransmitters that are involved in alcohol addiction. Hence a correction of gut liver brain axis using microbiome can be a milestone achieved not only for treatment of liver cirrhosis but also for helping alcohol addicts quit and live a healthy or at least a near healthy life.