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The stomach-brain axis.
The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be required instead of widely utilised opportunistic stool microbiome studies. In summary, it is now well established that there are important links between the brain and the stomach that have significant effects on gastric function. However, the stomach also influences the brain. Disturbances in the crosstalk between the stomach and the brain may manifest as functional GI disorders while disturbances in the stomach-brain communication may also result in an altered regulation of satiety and as a consequence may affect eating behaviour and mood. These observations may enable the identification of novel therapies targeted at the gastroduodenum that positively alter brain function and treat or prevent conditions such as obesity or functional gastrointestinal disorders.
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Changes to Gut Microbiota Following Systemic Antibiotic Administration in Infants.
Long-term antibiotic use can have consequences on systemic diseases, such as obesity, allergy, and depression, implicating the causal role of gut microbiome imbalance. However, the evaluation of the effect of antibiotics in early infancy on alterations to the gut microbiome remains poorly understood. This study aimed to evaluate the gut microbiome state in infancy following systemic antibiotic treatment. Twenty infants under 3 months of age who had received antibiotics for at least 3 days were enrolled, and their fecal samples were collected 4 weeks after antibiotic administration finished. Thirty-four age-matched healthy controls without prior exposure to antibiotics were also assessed. The relative bacterial abundance in feces was obtained via sequencing of 16 S rRNA genes, and alpha and beta diversities were evaluated. At the genus level, the relative abundance of Escherichia/Shigella and Bifidobacterium increased (p = 0.03 and p = 0.017, respectively) but that of Bacteroides decreased (p = 0.02) in the antibiotic treatment group. The microbiome of the antibiotic treatment group exhibited an alpha diversity lower than that of the control group. Thus, systemic antibiotic administration in early infancy affects the gut microbiome composition even after a month has passed; long-term studies are needed to further evaluate this.
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Lactobacillaceae-mediated eye-brain-gut axis regulates high myopia-related anxiety: from the perspective of predictive, preventive, and personalized medicine.
BACKGROUND: High myopia has become a major cause of blindness worldwide and can contribute to emotional deficits through its impact on the central nervous system. The potential crosstalk with gut microbiome positions high myopia as a valuable model for studying the eye-brain-gut axis, highlighting the intricate interplay between visual health, neurological function, and the gut microbiome. Understanding these connections is crucial from a predictive, preventive, and personalized medicine (PPPM) perspective, as it may reveal novel intervention targets for managing both visual and mental health. WORKING HYPOTHESIS AND METHODOLOGY: In our study, we hypothesized that visual stimuli associated with high myopia may lead to gut microecological dysregulation, potentially triggering mood disorders such as anxiety and depression. To test this hypothesis, we assessed genetic associations between high myopia (N = 50,372) and depression (N = 674,452) as well as anxiety (N = 21,761) using inverse variance weighted as the primary analytical method. We also investigated the potential mediating role of the gut microbiome (N = 18,340). The findings were validated in an independent cohort and summarized through meta-analysis. RESULTS: A genetic causal relationship between high myopia and anxiety was found (odds ratio [OR] = 8.76; 95% confidence interval [CI], 2.69-28.54; p = 3.16 × 10-4), with 20.3% of the effect mediated by the gut microbiome family Lactobacillaceae (β = 0.517; 95% CI, 0.104-1.090; p = 0.037). The analysis also showed a suggestive causal relationship between high myopia and depression (OR = 1.25; 95% CI, 1.00-1.57; p = 0.048). CONCLUSIONS: Our study shows that high myopia causes anxiety via the Lactobacillaceae family of the gut microbiome, supporting the eye-brain-gut axis concept. This underscores the need to shift from reactive to predictive, preventive, and personalized medicine (PPPM). Targeting Lactobacillaceae offers novel insights for early intervention and personalized treatment of high myopia-related anxiety and sheds light on interventions for other vision-related brain disorders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00387-z.
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Mechanisms of the effect of gut microbes on depression through the microbiota-gut-brain axis.
Depression is a significant public health issue which exerts profound psychological and social impacts on both individuals and society. However, existing therapeutic strategies often exhibit limited efficacy. Accumulating evidence underscores the vital role of gut microbiota in the pathophysiology of depression through the microbiota-gut-brain (MGB) axis. This involves multiple mechanisms, including short-chain fatty acid (SCFA) metabolism, communication via the vagal nerve, regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and immune-inflammatory interactions. This review provides a comprehensive review of the mechanisms through which gut microbiota influences depression via the MGB axis. It synthesizes recent achievements in this field and evaluates the potential of microbiome-targeted therapies for depression treatment. Furthermore, it outlines future research directions to establish a theoretical framework for novel therapeutic approaches and to foster the development of this area.
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Gut Microbiome Alterations, Mental Health, and Alcohol Consumption: Investigating the Gut-Brain Axis in Firefighters.
Firefighters across the world face higher risks of occupational hazards, such as exposure to chemicals, extreme heat, traumatic stressors, and intense physical demands, which can increase their vulnerability to a range of psychological and physiological difficulties. These challenges include the risk of developing chronic stress, depression, and post-traumatic stress disorder (PTSD), potentially leading to detrimental negative coping patterns such as alcohol abuse. The consequent health implications impact both short-term and long-term health and well-being. This study aimed to explore the relationship between mental health status, alcohol consumption patterns, and gut microbiome alterations in firefighters from two different regions-America and Korea. By investigating these relationships, we hope to gain insights into how repeated exposure to severe stressors impacts gut health. Healthy male firefighters (ages 21-50) and controls (matched sex, geography, and age) were recruited via flyers and snowball sampling in the United States and South Korea, resulting in 203 participants (102 firefighters and 101 controls). Firefighters reported significantly higher PTSD symptoms and depression and drank 2.3 times more alcohol than the control group. American firefighters reported more drinking than Koreans. There was a significant correlation between higher alcohol consumption and the likelihood of witnessing deaths by suicide. However, there were no correlations between alcohol consumption and PTSD symptom severity. There were associations between alcohol consumption patterns and aspects of the gut microbiome. This study highlights the mental health challenges faced by firefighters, including elevated rates of PTSD, depression, and alcohol consumption, with specific microbial imbalances linked to PTSD and alcohol use, emphasizing the role of the gut-brain axis.
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Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options.
The gut microbiota is critical for maintaining human health and the immunological system. Several neuroscientific studies have shown the significance of microbiota in developing brain systems. The gut microbiota and the brain are interconnected in a bidirectional relationship, as research on the microbiome-gut-brain axis shows. Significant evidence links anxiety and depression disorders to the community of microbes that live in the gastrointestinal system. Modified diet, fish and omega-3 fatty acid intake, macro- and micro-nutrient intake, prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, and 5-HTP regulation may all be utilized to alter the gut microbiota as a treatment approach. There are few preclinical and clinical research studies on the effectiveness and reliability of various therapeutic approaches for depression and anxiety. This article highlights relevant research on the association of gut microbiota with depression and anxiety and the different therapeutic possibilities of gut microbiota modification.
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Gut Microbiome: A Brief Review on Its Role in Schizophrenia and First Episode of Psychosis.
There is a growing body of evidence highlighting the role of gut microbiota as a biological basis of psychiatric disorders. The existing literature suggest that cognitive and emotional activities can be influenced by microbes through the microbiota-gut-brain axis and implies an association between alterations in the gut microbiome and several psychiatric conditions, such as autism, depression, bipolar disorder and psychosis. The aim of this review is to summarise recent findings and provide concise updates on the latest progress of the role of gut microbiota in the development and maintenance of psychiatric symptoms in schizophrenia and the first episode of psychosis. Despite the lack of consistent findings in regard to specific microbiome changes related to psychosis, the emerging literature reports significant differences in the gut microbiome of schizophrenic subjects compared to healthy controls and increasingly outlines the significance of an altered microbiome composition in the pathogenesis, development, symptom severity and prognosis of psychosis. Further human studies are, however, required, which should focus on identifying the drivers of microbiota changes in psychosis and establish the direction of causality between psychosis and microbiome alterations.
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Compendium of Bifidobacterium-based probiotics: characteristics and therapeutic impact on human diseases.
The human microbiota, a complex community of microorganisms residing in and on the human body, plays a crucial role in maintaining health and preventing disease. Bifidobacterium species have shown remarkable therapeutic potential across a range of health conditions, thus being considered optimal probiotic bacteria. This review provides insights into the concept of probiotics and explores the impact of bifidobacteria on human health, focusing on the gastrointestinal, respiratory, skeletal, muscular, and nervous systems. It also integrates information on the available genetic bases underlying the beneficial effects of each bifidobacterial probiotic species on different aspects of human physiology. Notably, Bifidobacterium-based probiotics have proven effective in managing gastrointestinal conditions such as constipation, antibiotic-associated diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Helicobacter pylori infections. These benefits are achieved by modulating the intestinal microbiota, boosting immune responses, and strengthening the gut barrier. Moreover, Bifidobacterium species have been reported to reduce respiratory infections and asthma severity. Additionally, these probiotic bacteria offer benefits for skeletal and muscular health, as evidenced by Bifidobacterium adolescentis and Bifidobacterium breve, which have shown anti-inflammatory effects and symptom relief in arthritis models, suggesting potential in treating conditions like rheumatoid arthritis. Furthermore, probiotic therapies based on bifidobacterial species have shown promising effects in alleviating anxiety and depression, reducing stress, and enhancing cognitive function. Overall, this review integrates the extensive scientific literature now available that supports the health-promoting applications of probiotic Bifidobacterium species and underscores the need for further research to confirm their clinical efficacy across different body systems.
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Orally administered selenium-containing α-D-1,6-glucan and α-D-1,6-glucan relief early cognitive deficit in APP/PS1 mice.
Alzheimer's disease (AD) is a complex, progressive and deadly disorder that exhibits various typical pathological characteristics. Till now no effective treatment has been found that can prevent or reverse AD. Here, the effects of 2 months of treatment with α-D-1,6-glucan (CPA) and selenium-containing α-D-1,6-glucan (Se-CPA) on early cognitive dysfunction and neuropathology were explored in the 3-month-old APP/PS1 transgenic mouse. The results of the Morris water maze and open-field test revealed that Se-CPA exerted more significant effects than CPA in improving cognitive function and depressive-like behavior by attenuating the oxidative stress, decreasing serum LPS level, downregulating the inflammation of astrocytes and microglia through inhibiting the activation of NLRP3 inflammasome, mitigating neuronal cells loss and improving synaptic plasticity. Moreover, Se-CPA exerted beneficial effects on reshaping gut microbiome by increasing the microbial α-diversity, enhancing the proportion of beneficial bacteria such as Akkermansia muciniphila and promoting the SCFAs concentration. These findings provide evidence that Se-CPA might be a potentially viable compound for AD prevention.
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Electroacupuncture alleviates comorbid obesity and depression via the gut-brain axis: orchestrating SCFA-producing bacteria and hippocampal synaptic plasticity.
INTRODUCTION: Comorbid obesity and depression (COMBD) represents a complex metabolic-neuropsychiatric challenge with limited therapeutic options. While Electroacupuncture (EA) is effective for both metabolic and mood disorders, the systemic mechanisms-particularly the interplay between the gut microbiome and hippocampal plasticity-remain elusive. METHODS: We established a COMBD rat model using a high-fat diet combined with chronic unpredictable mild stress (CUMS). An integrated multi-omics approach comprising 16S rDNA sequencing, LC-MS/MS serum metabolomics, and hippocampal transcriptomics was utilized to decipher the therapeutic mechanisms of EA. RESULTS: EA treatment significantly attenuated body weight gain and reversed depressive-like behaviors. Crucially, EA restructured the dysbiotic gut microbiota, specifically increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria. This microbial restoration was strongly correlated with a reprogrammed serum metabolic profile. In the hippocampus, transcriptomic analysis identified Cd74 as a pivotal upstream regulator modulated by EA. Furthermore, EA mitigated hippocampal oxidative stress and restored synaptic plasticity, evidenced by increased dendritic spine density and upregulated synaptic protein expression. CONCLUSION: Our findings suggest that EA ameliorates COMBD via a coordinated "Microbiota-Metabolism-Brain" axis. Specifically, EA creates a neuroprotective milieu by promoting beneficial SCFA-producing bacteria and regulating metabolic signals, which subsequently targets hippocampal Cd74 to restore synaptic plasticity. This study provides a novel mechanistic basis for the clinical application of EA in treating complex metabolic-mood comorbidities.