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Transcutaneous auricular vagus nerve stimulation improves depressive-like behaviors in CUMS rats through regulation of gut microbiome, serum metabolites, and immune factors.
BACKGROUND: Depression is associated with microbiota-gut-brain (MGB) axis dysregulation. Transcutaneous auricular vagus nerve stimulation (taVNS) has shown antidepressant effects and modulated gut microbiota, but its potential to alleviate depression specifically via modulation of the MGB axis remains largely unexplored. METHODS: Rats subjected to chronic unpredictable mild stress (CUMS) received taVNS for 3 weeks. We assessed depressive-like behaviors, gut microbiota, plasma metabolism, and inflammatory marker levels. Pearson correlation analyses examined relationships among these factors. RESULTS: taVNS significantly improved depressive behaviors in CUMS rats. It shifted gut microbiota composition, enriching beneficial Lactobacillus murinus, Bifidobacterium animalis, and Prevotellaceae while reducing harmful Bacteroidales and Romboutsia. Metabolomics revealed taVNS modulated plasma metabolism, especially metabolism of cofactor/vitamin, sphingolipid metabolism, amino and organic acid metabolism, increasing the levels of indole-3-lactic acid (ILA), riboflavin, sphingosine-1-phosphate (S1P), sphinganine-1-phosphate (Sa1P) and sphingosine (SP), and creatine. taVNS also reduced blood, hippocampus and prefrontal cortex inflammation. Pearson correlation analysis showed that alleviation of depressive behaviors positively correlated with Lactobacillus murinus, Bifidobacterium animalis, and plasma ILA, riboflavin, S1P, Sa1P, SP, and creatine and all these parameters inversely associated with pro-inflammatory factors. CONCLUSION: These findings indicate that taVNS may alleviate depression by enriching Lactobacillus murinus and Bifidobacterium animalis to enhance biosynthesis of microbiota-derived metabolites (ILA, riboflavin) and modulate host plasma metabolites (S1P, Sa1P, SP, creatine), thereby attenuating systemic and neuroinflammatory processes.
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Gut microbiome composition and diversity are related to human personality traits.
The gut microbiome has a measurable impact on the brain, influencing stress, anxiety, depressive symptoms and social behaviour. This microbiome-gut-brain axis may be mediated by various mechanisms including neural, immune and endocrine signalling. To date, the majority of research has been conducted in animal models, while the limited number of human studies has focused on psychiatric conditions. Here the composition and diversity of the gut microbiome is investigated with respect to human personality. Using regression models to control for possible confounding factors, the abundances of specific bacterial genera are shown to be significantly predicted by personality traits. Diversity analyses of the gut microbiome reveal that people with larger social networks tend to have a more diverse microbiome, suggesting that social interactions may shape the microbial community of the human gut. In contrast, anxiety and stress are linked to reduced diversity and an altered microbiome composition. Together, these results add a new dimension to our understanding of personality and reveal that the microbiome-gut-brain axis may also be relevant to behavioural variation in the general population as well as to cases of psychiatric disorders.
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The role of maternal gut microbiota in prenatal depression and offspring neurodevelopment.
Prenatal depression is a prevalent complication during pregnancy that not only adversely affects maternal mental health and elevates the risk of postpartum depression but also has enduring implications for offspring development. Alterations in the host metabolome and gut microbiome have been linked to the onset and progression of depression; however, the biological mechanisms underlying the association between maternal mood disorders and fetal brain development remain inadequately understood. Recent studies have associated prenatal depression and psychological stress with alterations in the maternal gut microbiota, microbial metabolism, and immune signaling. However, most human evidence remains observational, and it remains unclear whether these microbial alterations precede depressive symptoms, arise as a consequence of depression or psychological stress, or act as intermediate factors within the maternal gut-brain axis. These findings offer novel strategies for the prevention and treatment of threats to maternal-fetal health. This article systematically reviews recent advancements in research concerning the "microbiota-gut-brain" axis in the context of maternal-fetal health. It investigates the roles and mechanisms of gut microbiota through preclinical and clinical studies, assesses the feasibility of potential therapeutic strategies, and suggests directions for future research. The aim is to provide a theoretical foundation for interventions targeting maternal-fetal health in cases of prenatal depression.
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Permeability of the intestinal epithelial and blood-brain barriers as therapeutic targets in inflammatory depression.
Inflammation has emerged as a compelling causal contributor to depression, serving both as a biological pathway underlying specific depressive symptoms (notably anhedonia, fatigue, and cognitive difficulties) and as a defining feature in a subtype of this disorder characterized by elevated levels of circulating cytokines. Understanding when and how immune dysfunction results in depression within clinical trials is needed to advance biomarker-guided clinical research and to accelerate novels treatments for those suffering from depression. In this context, gut microbes and intestinal epithelial barrier (IEB) integrity directly influence systemic cytokine levels and peripheral immune activation-these immune signals, in turn, modulate neural circuits involved in mood, reward, and stress reactivity through several pathways. Many of these signals converge on the blood-brain barrier (BBB), the permeability of which regulates the entry of peripheral cytokines and immune cells into the central nervous system and consequently shapes neuroinflammatory responses that contribute to depressive symptoms. In this narrative review, we contend that immune-gut-brain system is critical for understanding mechanisms and potential treatments for inflammatory depression. We synthesize evidence linking inflammation to IEB and BBB permeability, summarize barrier biomarkers relevant for depression, and highlight future directions of research that focus on fortifying dual barrier dysfunction as a novel intervention target for inflammatory depression. By considering the inflammatory mechanisms that shape IEB and BBB integrity, the field will be positioned to identify upstream drivers of these sources of inflammation, refine mechanistic models of transdiagnostic symptoms relevant to inflammation (anhedonia, fatigue, executive dysfunction), and develop more targeted or personalized intervention strategies for those suffering from these conditions.
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Gut microbiome metabolites as key actors in atherosclerosis co-depression disease.
Cardiovascular diseases, mainly characterized by atherosclerosis (AS), and depression have a high comorbidity rate. However, previous studies have been conducted under a single disease, and there is a lack of studies in comorbid states to explore the commonalities in the pathogenesis of both diseases. Modern high-throughput technologies have made it clear that the gut microbiome can affect the development of the host's own disorders and have shown that their metabolites are crucial to the pathophysiology of AS and depression. The aim of this review is to summarize the current important findings on the role of gut microbiome metabolites such as pathogen-associated molecular patterns, bile acids, tryptophan metabolites, short-chain fatty acids, and trimethylamine N -oxide in depression and AS disease, with the aim of identifying potential biological targets for the early diagnosis and treatment of AS co-depression disorders.
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Atypical Cognitive Impairment and Recovery in Two Colorectal Cancer Patients.
Cognitive impairment in cancer patients can be caused by various factors; in approximately 30% of cancer patients, the symptoms appear before starting treatment. Paraneoplastic limbic encephalitis (PLE) is a rare disease associated with an autoimmune response, and is characterized by memory loss, depression, and personality changes; it is one of the potential causes of cognitive dysfunction in cancer patients. Two patients were previously diagnosed with mild cognitive impairment and maintained clinical stability; after suffering a rapid change in personality and sudden cognitive decline, colorectal cancer was diagnosed within a few months. The patients did not meet the diagnostic criteria for PLE in several tests. The symptoms improved after the underlying cancer was treated, and the patients returned to their previous stable state. Sudden cognitive impairment may appear as an early cancer symptom, and PLE is considered an atypical cause for these symptoms. However, in patients with unexplained PLE-like symptoms who do not meet the diagnostic criteria for PLE, probable etiologies to be considered are the gut-brain connection, CD8+ T-cell-mediated limbic encephalitis, and somatic mutations in dementia-related genes. Currently, few studies have investigated these symptoms, and further research will offer significant therapeutic strategies for cognitive impairment in cancer patients.
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Association of short-chain fatty acid-producing gut microbiota and dietary habits with maternal depression in a subclinical population.
The prevalence of postpartum mental illness is steadily increasing, a tendency that was exacerbated by the COVID-19 pandemic. Recent studies show that maternal depression is no longer confined to the perinatal period, and this necessitates long-term assessment and support for maternal mental health. It is critical to identify the factors that are related to depression among mothers, and this requires the development of integrated mental and physical health care encompassing both psychological aspects and intestinal microbiota, physical conditions, and dietary habits. Studies conducted in western countries have examined the association between gut microbiota and depressive disorders. However, little is known concerning postpartum mothers in healthy populations. In addition, even in healthy populations, some mothers will have severe depression. This is because mothers in Japan are typically hesitant to disclose psychiatric symptoms and tend not to consult specialists. Therefore, we conducted a cross-sectional study to investigate the association of intestinal microbiota, physical condition, and dietary habits with depressed mood in healthy mothers in Japan. We found that microbiome diversity (Shannon α) and relative abundance of butyrate-producing bacteria (e.g. Lachnospira, Faecalibacterium, and Subdoligranulum), obtained using 16S rRNA gene-sequencing analysis, were associated with high levels of depressive mood. Mothers who have this attribute showed poorer sleep quality and worse physical condition than mothers with low levels of depressive mood. The evaluation of dietary habits suggested that dietary patterns high in soy products, fermented food, seaweed, and mushrooms, as well as vegetables, are beneficial for depression and intestinal microbiota (e.g. Lachnospira, Agathobacter, and Subdoligranulum).
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The Intertwining Roads between Psychological Distress and Gut Microbiota in Inflammatory Bowel Disease.
Inflammatory bowel disease represents one of the most life-altering gastrointestinal pathologies, with its multifactorial nature and unclear physiopathology. The most relevant clinical forms, ulcerative colitis and Crohn's disease, clinically manifest with mild to severe flares and remission periods that alter the patient's social, familial and professional integration. The chronic inflammatory activity of the intestinal wall determines severe modifications of the local environment, such as dysbiosis, enteric endocrine, nervous and immune system disruptions and intestinal wall permeability changes. These features are part of the gastrointestinal ecosystem that modulates the bottom-to-top signaling to the central nervous system, leading to a neurobiologic imbalance and clinical affective and/or behavioral symptoms. The gut-brain link is a bidirectional pathway and psychological distress can also affect the central nervous system, which will alter the top-to-bottom regulation, leading to possible functional digestive symptoms and local inflammatory responses. In the middle of this neuro-gastrointestinal system, the microbiome is a key player, as its activities offer basic functional support for both relays. The present article presents current scientific information that links the pathophysiology and clinical aspects of inflammatory bowel disease and psychiatric symptomatology through the complex mechanism of the gut-brain axis and the modulatory effects of the gut microbiota.
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Assessing the long-term effects of microbial therapeutics as treatment within psychiatry: a systematic review.
BACKGROUND: The management and treatment of psychiatric disorders by manipulating the gut microbiome and utilizing microbial therapeutics, via modulation of the gut-brain-axis, has been a rapidly growing field of research. Given the novelty of using microbial therapeutics within psychiatry, a growing number of studies have investigated their use as treatment for various psychiatric disorders and symptoms. However, few studies have explored the longitudinal efficacy of these treatments. This review aims to summarize the findings of any studies assessing the long-term effects of gut-related interventions on mood and psychiatric symptoms. METHODS: A systematic search of 4 databases (Embase, PsycINFO, Medline, Web of Science) from inception to May 28, 2025, informed by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and using key words relating to microbial therapeutics, psychiatric disorders, and long-term effects was conducted. Findings were included or excluded using pre-determined eligibility criteria such as being been written in English and published by a peer-reviewed journal, assessed for quality using the Cochrane Handbook for Systematic Reviews of Interventions Risk of Bias tool, and qualitatively evaluated. RESULTS: The search yielded 4175 studies, of which 1274 duplicates were removed. All remaining studies underwent abstract screening, from which 70 records were full-text screened and a total of ten clinical studies (n = 10) met eligibility criteria and were included in the review. The majority of studies explored the effects of microbial therapeutics such as fecal microbiota transplant and probiotics, as treatment for disorders of the gastrointestinal tract as the primary scope, with additional outcome measures assessing psychiatric well-being. The review presented with mixed findings: many studies reported a sustained improvement in symptoms of depression and anxiety ranging from 3- to 18-months post-treatment, while others reported the opposite with no sustained long-term improvement in mood-related symptoms. There was also a lack of consistency across follow-up duration between studies, making it difficult to compare findings. CONCLUSIONS: Overall, this review highlighted the need for more placebo-controlled studies with larger sample sizes to effectively evaluate the longitudinal potential of microbial therapeutics as treatment for mood-disturbances and psychiatric symptoms. With consideration for the limitations of this field, these results provide evidence that there may be long-term benefits of targeting the gut microbiome as treatment for mood-related disturbances.
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Prenatal Depression, Breastfeeding, and Infant Gut Microbiota.
Depressive symptoms are common during pregnancy and are estimated to affect 7-20% of pregnant women, with higher prevalence found in those with a prior history of depression, in ethnic minorities, and those with increased exposure to stressful life events. Maternal depression often remains undiagnosed, and its symptoms can increase adverse health risks to the infant, including impaired cognitive development, behavioral problems, and higher susceptibility to physical illnesses. Accumulating research evidence supports the association between maternal physical health elements to infant gut health, including factors such as mode of delivery, medication, feeding status, and antibiotic use. However, specific maternal prenatal psychosocial factors and their effect on infant gut microbiota and immunity remains an area that is not well understood. This article reviews the literature and supplements it with new findings to show that prenatal depression alters: (i) gut microbial composition in partially and fully formula-fed infants at 3-4 months of age, and (ii) gut immunity (i.e., secretory Immunoglobulin A) in all infants independent of breastfeeding status. Understanding the implications of maternal depression on the infant gut microbiome is important to enhance both maternal and child health and to better inform disease outcomes and management.