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Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting.
RATIONALE: There is a worldwide prevalence of generalized anxiety and major depressive disorders (MDD). Gut⁻brain axis dysfunction, antibacterial activity, and modulatory effects of antidepressants toward intestinal bacteria have been shown both in vitro and in vivo. OBJECTIVES: In this study, we aimed to investigate the effects of hospital stay, including escitalopram administration, on gut microbiota in patients with depressive episodes. METHODS: After admission to the hospital and 7-days washout from all medications the composition of fecal microbiota samples was evaluated at baseline (W0) and after 6 weeks (W6), using 16S rRNA sequencing. The study was conducted on 17 inpatients (52.9% females), who followed the same daily hospital routine, including a standard diet and received 5⁻20 mg daily doses of escitalopram. RESULTS: At the end of treatment (W6), no change was observed in the Chao1 index. However, Shannon (median (Q1⁻Q3): W0 2.78 (2.67⁻3.02) vs. W6 3.11 (2.80⁻3.30)), and inverse Simpson (median (Q1⁻Q3): W0 9.26 (7.26⁻13.76) vs. W6 12.13 (9.17⁻15.73)) indices increased significantly compared to baseline values (False Discovery Rate p (q) = 0.031 and q = 0.011, respectively). We also found that between-subject W0 Bray⁻Curtis dissimilarities were significantly higher than W0⁻W6 within-subject dissimilarities (median (Q1⁻Q3): 0.68 (0.56⁻0.77) vs. 0.38 (0.35⁻0.52), two sided Mann⁻Whitney test p < 0.00001. The within-subject dissimilarities did not depend on sex, age, BMI, illness duration and a daily dose of escitalopram. No significant differences between taxa levels, at the studied time points, were observed when adjusted for multiple hypotheses testing procedures. CONCLUSIONS: We conclude that a six-week treatment in a psychiatric hospital setting resulted in increased alpha biodiversity in fecal microbiota, however its causal relationship with patients' mental health was not proved. We have also found that individual microbiome stability was not affected by hospitalization.
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Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut-Brain Axis.
Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota-gut-brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut-brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut-brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.
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Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome.
BACKGROUND: Diet is fundamental to the care of irritable bowel syndrome (IBS). However, some approaches are not appropriate for individuals experiencing psychological symptoms. AIMS: To assess feasibility of a Mediterranean diet in IBS and its impact on gastrointestinal and psychological symptoms. METHODS: We recruited adults with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms to an unblinded 6-week randomised controlled trial. Patients were randomised to Mediterranean diet counselling or habitual diet. We collected gastrointestinal and psychological symptom data, dietary data and stool samples for metagenomic sequencing. RESULTS: We randomised 59 individuals (29 Mediterranean diet, 30 control); 48 completed the study. The Mediterranean Diet Adherence Screener score was higher in the Mediterranean diet group than controls at week 6 (7.5 [95% CI: 6.9-8.0] vs. 5.7 [5.2-6.3], p < 0.001), and there was a greater score increase than controls (2.1 [95% CI: 1.3-2.9] vs. 0.5 [95% CI: 0.1-1.0], p = 0.004), demonstrating Mediterranean diet feasibility. There was a greater proportion of gastrointestinal symptom responders in the Mediterranean diet group than controls (24/29, 83% vs. 11/30, 37%, p < 0.001) and depression responders (15/29, 52% vs. 6/30 20%, p = 0.015). There was no difference in FODMAP intake at week 6 (p = 0.51). Gastrointestinal adverse events were similar (p = 0.588). There were no differences in change in microbiome parameters between groups. CONCLUSIONS: A Mediterranean diet is feasible in IBS and leads to improvement in gastrointestinal and psychological symptoms. Although this study was unblinded, these findings together with the broader benefits of the Mediterranean diet, provide strong impetus for future research in IBS. Australia New Zealand Clinical Trials Registry: ACTRN12620001362987.
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Decoding the neurocircuitry of gut feelings: Region-specific microbiome-mediated brain alterations.
Research in the last decade has unveiled a crucial role for the trillions of microorganisms that reside in the gut in influencing host neurodevelopment across the lifespan via the microbiota-gut-brain axis. Studies have linked alterations in the composition, complexity, and diversity of the gut microbiota to changes in behaviour including abnormal social interactions, cognitive deficits, and anxiety- and depressive-like phenotypes. Moreover, the microbiota has been linked with neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Interestingly, there appears to be specific brain regions governing the neurocircuitry driving higher cognitive function that are susceptible to influence from manipulations to the host microbiome. This review will aim to elucidate the region-specific effects mediated by the gut microbiota, with a focus on translational animal models and some existing human neuroimaging data. Compelling preclinical evidence suggests disruption to normal microbiota-gut-brain signalling can have detrimental effects on the prefrontal cortex, amygdala, hippocampus, hypothalamus, and striatum. Furthermore, human neuroimaging studies have unveiled a role for the microbiota in mediating functional connectivity and structure of specific brain regions that can be traced back to neurocognition and behavioural output. Understanding these microbiota-mediated changes will aid in identifying unique therapeutic targets for treating neurological disorders associated with these regions.
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Changes in respiratory and gut microbiota in asthma and depression associate with disease markers.
Asthma is heterogeneous and frequently accompanied by depression, affecting disease mechanisms and management. Both asthma and depression have been associated with inflammation and microbiota alterations, but their combined impact on microbial compositions remains unclear. Our exploratory study analyzed lung and gut microbiota in patients with asthma and depression to identify associations between microbiota composition and disease markers. This cross-sectional study included 20 healthy controls, 20 patients with asthma, and 20 patients with asthma and comorbid depression. Participants underwent clinical characterization and assessment of asthma control, depression, anxiety, and perceived stress. Induced sputum and fecal samples were collected for microbiota analysis, and inflammatory cytokines were measured in serum and sputum. Microbial profiling was performed using 16S rRNA gene sequencing. Lung function and FeNO levels were comparable between all groups. Asthma control scores were lower, and psychological scores were significantly higher in patients with asthma and comorbid depression compared with asthma alone and controls. Despite similar alpha and beta diversity across groups, sputum and fecal microbiota, particularly of healthy controls and comorbid patients, significantly differed in genus-level taxonomic composition. Correlation analyses demonstrated associations between clinical and psychological parameters and microbial profiles, including a consistent negative correlation between psychological scores and Neisseria abundance in both sputum and fecal samples. Asthma with comorbid depression is associated with distinct alterations in respiratory and gut microbiota, including reduced Neisseria perflava abundance correlating with psychological symptom severity.IMPORTANCEAsthma and depression frequently coexist, yet the potential contribution of microbial alterations to this comorbidity remains poorly understood. Because both respiratory and gut microbiota have been implicated in immune regulation and disease pathophysiology, characterizing microbiota patterns associated with asthma and depression may provide new insights into the biological links between these conditions. In this exploratory study, we investigated respiratory and gut microbiota in individuals with asthma, with and without comorbid depression, and healthy controls. Genus-level community composition differed between groups, particularly between controls and patients with asthma and depression. Notably, reduced abundance of Neisseria perflava in sputum and fecal samples was consistently associated with greater psychological symptom severity. These findings suggest that asthma accompanied by depression is associated with distinct alterations in microbial communities at multiple body sites. Further studies are warranted to determine whether such microbiota-psychological associations contribute to disease mechanisms or may serve as biomarkers of asthma-depression comorbidity.
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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.