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Anxiety-like Behavior in Female Sprague Dawley Rats Associated with Cecal Clostridiales.
The relationship between the microbiota profile and exposure to stress is not well understood. Therefore, we used a rat model of unpredictable chronic mild stress (UCMS) to investigate this relationship. Depressive-like behaviors were measured in Female Sprague Dawley rats using the sucrose preference test and the Porsolt swim test. Anxiety-like behaviors were measured with the light-dark box test. Fecal corticosterone, cecal microbiota (composition and organic acids), plasma gut permeability (lipopolysaccharide-binding protein, LBP) and plasma inflammation (12 cytokines) markers were measured. Atypical behaviors were observed in female rats following UCMS, but no depressive-like behaviors were observed. Circulating concentrations of cytokines granulocyte-macrophage colony-stimulating factor and cytokine-induced neutrophil chemoattractant 1 were higher in UCMS-exposed female rats; plasma LBP and cecal organic acid levels remained unchanged. Our results reflect a resilient and adaptive phenotype for female SD rats. The relative abundance of taxa from the Clostridiales order and Desulfovibrionaceae family did, however, correlate both positively and negatively with anxiety-like behaviors and plasma cytokine concentrations, regardless of UCMS exposure, supporting the brain-to-gut influence of mild anxiety with a microbiota profile that may involve inflammatory pathways.
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Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders.
Over the last 10 years, there has been a growing interest in the relationship between gut microbiota, the brain, and neurologic-associated affections. As multiple preclinical and clinical research studies highlight gut microbiota's potential to modulate the general state of health state, it goes without saying that gut microbiota plays a significant role in neurogenesis, mental and cognitive development, emotions, and behaviors, and in the progression of neuropsychiatric illnesses. Gut microbiota produces important biologic products that, through the gut-brain axis, are directly connected with the appearance and evolution of neurological and psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, and epilepsy. This study reviews recent research on the link between gut microbiota and the brain, and microbiome's role in shaping the development of the most common neurological and psychiatric illnesses. Moreover, special attention is paid to the use of probiotic formulations as a potential non-invasive therapeutic opportunity for prevention and management of neuropsychiatric-associated affections.
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Plant protein, fibre and physical activity solutions to address poor appetite and prevent undernutrition in older adults: study protocol for the APPETITE randomised controlled trial.
Reduced appetite with ageing is a key factor that may increase risk of undernutrition. The objective of this study is to determine the impact of innovative plant protein fibre (PPF) products within a personalised optimised diet (PD), a physical activity (PA) programme, and their combination on appetite, and other nutritional, functional and clinical outcomes in community-dwelling older adults in a multi-country randomised controlled intervention trial. One hundred and eighty community-dwelling adults (approximately sixty per trial centre in Germany, Ireland and Italy) aged 65 years and over will be recruited to participate in a 12-week, parallel-group, controlled trial. Participants will be randomised into one of four groups: 1, PD (incorporating two PPF products): 2, PA; 3, PD + PA; and 4, no intervention (control). The primary outcome is appetite measured by visual analogue scales and energy intake from an ad libitum test meal. Secondary outcomes include fasting and postprandial appetite-related gut hormones, Simplified Nutritional Appetite Questionnaire score, body composition, cardiorespiratory fitness, muscle strength, physical function and PA. In addition, self-efficacy, cognitive status, dietary restraint, depressive symptoms and compliance and acceptability of the intervention will be assessed. Metabolomic profiles, RMR, muscle motor unit properties and gut microbiome will also be assessed to explore potential underlying mechanisms. This multi-centre randomised controlled trial will advance knowledge on how PD (incorporating PPF products), PA and their combination influence appetite, nutritional status and related health outcomes in community-dwelling older adults and contribute to the prevention of undernutrition. Trial registration: Clinical Trials.gov Registry NCT05608707 (registered on 2 November 2022). Protocol Version: NCT05608707 Version 4 (registered on 29 September 2023).
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Microbiota-derived psychedelics: Lessons from COVID-19.
Emil Kraepelin believed that dementia praecox, the disorder we now call schizophrenia, was caused by the brain being poisoned with toxins generated in other parts of the body, especially the mouth, intestine or genitals. In this regard, Kraepelin hinted at the microbiome and conceptualized microbial molecules as drivers of severe psychiatric illness. However, it was not until the coronavirus disease (COVID-19) pandemic that Kraepelin's paradigm gained traction, particularly because this virus was associated with both gut barrier disruption and new-onset psychosis.Likewise, despite numerous studies linking severe psychiatric illness to genomic damage and dysfunctional DNA repair, this pathogenetic mechanism was underappreciated before the COVID-19 pandemic. The use of the psychotomimetic anesthetic, ketamine, for treatment-resistant depression has reawakened the interest in endogenous serotonergic hallucinogens, especially tryptamine and N,N-dimethyltryptamine (DMT), which are beneficial for depression but associated with psychosis.In this editorial, we take a closer look at the role of the microbiome in psychopathology, attempting to answer 2 questions:1. Why may psychosis-predisposing serotonergic hallucinogens alleviate depression?2. Are microbiota-derived psychedelics part of an inbuilt antidepressant system similar to endogenous opioids?
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Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms.
Symptoms of fatigue, social withdrawal and mood disturbances are commonly encountered in patients with chronic liver disease and have a detrimental effect on patient quality of life. Treatment options for these symptoms are limited and a current area of unmet medical need. In this review, we will evaluate the potential mechanistic avenues within the gut-liver-brain axis that may be altered in the setting of chronic liver disease that drive the development of these symptoms. Both clinical and pre-clinical studies will be highlighted as we discuss how perturbations in host immune response, microbiome, neural responses, and metabolites composition can affect the central nervous system.
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Metabolic Dysfunction in Psychiatric Disorders: A Narrative Review of Shared Pathways Between Mental Illness and Cardiometabolic Disease.
Psychiatric disorders and cardiometabolic disease (CMD) frequently coexist and contribute to substantial morbidity, premature mortality, and reduced quality of life. Although this association is increasingly recognized, the shared biological and clinical pathways linking mental illness with metabolic dysfunction remain incompletely defined. This article is a narrative review that examines recent evidence on mechanisms connecting depression, anxiety, schizophrenia, severe mental illness (SMI), obesity, insulin resistance, diabetes, dyslipidemia, hypertension, and cardiovascular disease. A narrative review approach was used, with literature identified from major biomedical databases and prioritized according to relevance to shared psychiatric-metabolic mechanisms, clinical significance, recency, and methodological strength. The review focuses on chronic low-grade inflammation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, insulin resistance, oxidative stress, mitochondrial dysfunction, altered brain energy metabolism, gut microbiome disruption, sleep and circadian disturbance, psychotropic medication effects, and behavioral and social determinants. Current evidence suggests that psychiatric and cardiometabolic disorders are associated through bidirectional and overlapping pathways rather than a single causal mechanism. Metabolic dysfunction may be associated with worsening psychiatric symptoms through inflammatory, neuroendocrine, and neurotrophic effects, while psychiatric illness may increase cardiometabolic risk (CMR) through stress biology, lifestyle factors, medication exposure, and fragmented healthcare access. Antipsychotic-associated weight gain and glucose-lipid abnormalities remain important, but metabolic changes may also precede long-term treatment exposure, particularly in psychotic disorders. These findings support routine metabolic screening, early risk stratification, individualized psychotropic prescribing, lifestyle intervention, and integrated care involving psychiatry, primary care, endocrinology, cardiology, nutrition, and behavioral health services. Future longitudinal studies and randomized trials are needed to clarify causality and evaluate interventions that improve both psychiatric and cardiometabolic outcomes. Metabolic health should be considered a core component of psychiatric assessment and management.
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Bifidobacteria modulate cognitive processes in an anxious mouse strain.
Increasing evidence suggests that a brain-gut-microbiome axis exists, which has the potential to play a major role in modulating behaviour. However, the role of this axis in cognition remains relatively unexplored. Probiotics, which are commensal bacteria offering potential health benefit, have been shown to decrease anxiety, depression and visceral pain-related behaviours. In this study, we investigate the potential of two Bifidobacteria strains to modulate cognitive processes and visceral pain sensitivity. Adult male BALB/c mice were fed daily for 11 weeks with B. longum 1714, B. breve 1205 or vehicle treatment. Starting at week 4, animals were behaviourally assessed in a battery of tests relevant to different aspects of cognition, as well as locomotor activity and visceral pain. In the object recognition test, B. longum 1714-fed mice discriminated between the two objects faster than all other groups and B. breve 1205-fed mice discriminated faster than vehicle animals. In the Barnes maze, B. longum 1714-treated mice made fewer errors than other groups, suggesting a better learning. In the fear conditioning, B. longum 1714-treated group also showed better learning and memory, yet presenting the same extinction learning profile as controls. None of the treatments affected visceral sensitivity. Altogether, these data suggest that B. longum 1714 had a positive impact on cognition and also that the effects of individual Bifidobacteria strains do not generalise across the species. Clinical validation of the effects of probiotics on cognition is now warranted.
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A genetic association study reveals the relationship between the oral microbiome and anxiety and depression symptoms.
BACKGROUND: Growing evidence supports that alterations in the gut microbiota play an essential role in the etiology of anxiety, depression, and other psychiatric disorders. However, the potential effect of oral microbiota on mental health has received little attention. METHODS: Using the latest genome-wide association study (GWAS) summary data of the oral microbiome, polygenic risk scores (PRSs) of 285 salivary microbiomes and 309 tongue dorsum microbiomes were conducted. Logistic and linear regression models were applied to evaluate the relationship between salivary-tongue dorsum microbiome interactions with anxiety and depression. Two-sample Mendelian randomization (MR) was utilized to compute the causal effects between the oral microbiome, anxiety, and depression. RESULTS: We observed significant salivary-tongue dorsum microbiome interactions related to anxiety and depression traits. Significantly, one common interaction was observed to be associated with both anxiety score and depression score, Centipeda periodontii SGB 224 × Granulicatella uSGB 3289 (P depressionscore = 1.41 × 10-8, P anxietyscore = 5.10 × 10-8). Furthermore, we detected causal effects between the oral microbiome and anxiety and depression. Importantly, we identified one salivary microbiome associated with both anxiety and depression in both the UKB database and the Finngen public database, Eggerthia (P IVW - majordepression - UKB = 2.99 × 10-6, P IVW - Self - reportedanxiety/panicattacks - UKB = 3.06 × 10-59, P IVW - depression - Finngen = 3.16 × 10 , - 16 P IVW - anxiety - Finngen = 1.14 × 10-115). CONCLUSION: This study systematically explored the relationship between the oral microbiome and anxiety and depression, which could help improve our understanding of disease pathogenesis and propose new diagnostic targets and early intervention strategies.
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Exploring the novel protein drug target BAG33339.1 of Porphyromonas gingivalis: an integrative subtractive proteomics and structural dynamics study.
Porphyromonas gingivalis, a gram-negative, bacterium interacts favourably with host subgingival biofilms to cause adult tooth decay and loss. Consequently, the host is infested with an uncontrollable microbial community and a compromised immune system, ultimately leading to tissue damage and bone resorption. P. gingivalis has also been known to cause cardiovascular and metabolic diseases, Alzheimer's disease, depression, prostate and digestive system cancer, rheumatoid arthritis, and adverse pregnancy outcomes with high detection frequencies. Rising concerns in the recent past, highlight the inefficiency of antibiotics and antiseptics in the treatment of P. gingivalis-related infections. Hence, the current scenario impels the discovery of an alternative therapeutic avenue against P. gingivalis-infections. To elucidate the unidentified bacterial mechanisms of infection, we screened a non-homolog of the host and gut microbiome as a novel druggable target from 173 essential hypothetical proteins of P.gingivalis (BAG33339.1). BAG33339.1 was an inner membrane protein with a hydrophobic N-terminal transmembrane helix and a primarily reconfiguring C-terminal helical region (Y36 to E52) while the residues (downstream of Lys45) lay in the disordered region. Frustration index coupled with the mutation matrix showed the steadiness of the transmembrane helix and dynamicity of the C-terminal residues finally yielding a 'U'-shaped protein conformation. The tendency of the disordered C-terminal residues was to generate P. gingivalis variants. The overall conformational stability was determined by equilibrating RMSD, Rg and SASA values corroborated by increasing H-bonds and helix settling. Targeting the ligand binding pockets of BAG33339.1 would guide future endeavours to tackle P. gingivalis interaction with host systems.
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Targeting the microbiome-gut-brain axis for improving cognition in schizophrenia and major mood disorders: A narrative review.
Cognitive impairment has been consistently found to be a core feature of serious mental illnesses such as schizophrenia and major mood disorders (major depression and bipolar disorder). In recent years, a great effort has been made in elucidating the biological causes of cognitive deficits and the search for new biomarkers of cognition. Microbiome and gut-brain axis (MGB) hormones have been postulated to be potential biomarkers of cognition in serious mental illnesses. The main aim of this review was to synthesize current evidence on the association of microbiome and gut-brain hormones on cognitive processes in schizophrenia and major mood disorders and the association of MGB hormones with stress and the immune system. Our review underscores the role of the MGB axis on cognitive aspects of serious mental illnesses with the potential use of agents targeting the gut microbiota as cognitive enhancers. However, the current evidence for clinical trials focused on the MGB axis as cognitive enhancers in these clinical populations is scarce. Future clinical trials using probiotics, prebiotics, antibiotics, or faecal microbiota transplantation need to consider potential mechanistic pathways such as the HPA axis, the immune system, or gut-brain axis hormones involved in appetite control and energy homeostasis.