RESUMEN
Evidence shows that the composition of the gut microbiota (GM) is associated with depression and anxiety disorders. However, the causal relationship between them remains controversial. To investigate the potential causal relationship between the GM and depression/anxiety disorders and to identify specific bacterial taxa, we conducted a 2-sample Mendelian randomization (MR) analysis on the gut microbiome implicated in depression and anxiety disorders. We incorporated summary data from genome-wide association studies (GWAS) of the microbiome derived from 7738 individuals in the Dutch Microbiome Project and 18,340 individuals in the MiBioGen consortium as our exposure variable. Concurrently, the GWAS of depression and anxiety disorders was employed as our outcome variable. The principal estimates were procured using the inverse-variance weighted test complemented by 4 robust methods: MR Egger, weighted median, simple mode, and weighted mode. In addition, we performed comprehensive sensitivity and directionality analyses. The results showed that 5 bacterial taxa were positively correlated with depression, 6 were negatively correlated; 5 were positively correlated with anxiety disorders, and 11 were negatively correlated. This study provides new insights into the connection between the GM and the pathogenesis of depression and anxiety disorders and offers new perspectives for the diagnosis and treatment of these disorders.
Asunto(s)
Trastornos de Ansiedad , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/genética , Trastorno Depresivo/microbiología , Trastorno Depresivo/genética , Depresión/microbiologíaRESUMEN
The gut microbiome is a vast, variable, and largely unexplored component of human biology that sits at the intersection of heritable and environmental factors, and represents a rich source of novel chemistry that is already known to be compatible with the human body. This alone would make it a promising place to search for new therapeutics, but recent work has also identified gut microbiome abnormalities in patients with a number of psychiatric disorders, including anxiety disorders-suggesting that not only treatments, but cures may lie therein. Here, we'll discuss two known "para-endogenous" anxiolytics-γ-hydroxybutyrate and the neurosteroid allopregnanolone-which have recently been discovered to be produced by the microbiome.
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Ansiolíticos , Microbioma Gastrointestinal , Humanos , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/metabolismo , Pregnanolona/uso terapéutico , Pregnanolona/farmacología , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/microbiologíaRESUMEN
Climate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.
Asunto(s)
Ansiedad , Ácidos y Sales Biliares , Disbiosis , Microbioma Gastrointestinal , Calor , Animales , Masculino , Ratones , Ácidos y Sales Biliares/metabolismo , Humanos , Disbiosis/microbiología , Ansiedad/microbiología , Ratones Endogámicos C57BL , Humedad , Ácido Litocólico/metabolismo , Lactobacillus , Encéfalo/metabolismo , FN-kappa B/metabolismo , ARN Ribosómico 16S/genética , Modelos Animales de Enfermedad , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/etiología , Transducción de Señal , Citocinas/metabolismoRESUMEN
BACKGROUND: There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). METHODS: Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran's Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy. RESULT: We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses. CONCLUSION: Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.
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Trastornos de Ansiedad , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Microbioma Gastrointestinal/genética , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/microbiología , Eje Cerebro-Intestino/genéticaRESUMEN
OBJECTIVE: Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity. METHODS: The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status. RESULTS: Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas, CHKCI001, Clostridium sensu stricto 1, Oscillibacter, and Flavonifractor; social processes with Sellimonas; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all pFDR < 0.05). CONCLUSION: Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways.
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Microbioma Gastrointestinal , Trastornos Mentales , Humanos , Microbioma Gastrointestinal/fisiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Trastornos Mentales/microbiología , Trastorno del Espectro Autista/microbiología , Trastorno por Déficit de Atención con Hiperactividad/microbiología , Trastornos de Ansiedad/microbiología , Trastornos Relacionados con Sustancias/psicología , Adulto Joven , Trastornos del Humor/microbiología , Trastornos del Humor/psicologíaRESUMEN
BACKGROUND: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD,1 normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT,2 has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis. METHODS: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported. RESULTS: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4 %) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40 %). LIMITATIONS: Limitations include potential bias in study selection, study methods of analysis, and generalization of results. CONCLUSIONS: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment.
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Trastornos de Ansiedad , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiología , Trastornos de Ansiedad/terapia , Trastornos de Ansiedad/microbiología , Eje Cerebro-Intestino/fisiologíaRESUMEN
Introduction: Generalized anxiety disorder (GAD) is one of the most enduring anxiety disorders, being associated with increased systemic inflammation. However, the trigger and mechanisms underlying the activation of inflammatory cytokine responses in GAD remain poorly understood. Materials and methods: We characterized the ear canal microbiome in GAD patients through 16S rRNA gene sequencing and metagenomic sequencing and identified the serum inflammatory markers in GAD patients. Spearman correlations were applied to test the relationship between the microbiota changes and systemic inflammation. Results: Our findings showed the higher microbial diversity, accompanied with the significantly increased abundance of Proteobacteria, and decreased abundance of Firmicutes in the ear canal of GAD participants compared to that of the age- and sex-matched healthy controls (HC). Metagenomic sequencing showed that Pseudomonas aeruginosa were significantly increased at species-level in GAD patients. Furthermore, we observed the relative abundance of Pseudomonas aeruginosa was positively associated with elevated systemic inflammatory markers and the severity of disease, suggesting that these ear canal microbiota alterations might be correlated with GAD by activating the inflammatory response. Conclusions: These findings indicate that microbiota-ear-brain interaction via upregulating inflammatory reaction involve in the development of GAD, as well as suggest that ear canal bacterial communities may be a target for therapeutic intervention.
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Citocinas , Microbiota , Humanos , ARN Ribosómico 16S , Trastornos de Ansiedad/microbiología , Encéfalo , InflamaciónRESUMEN
Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (ß = - 0.009, P = 2.2 × 10-3), G_Akkermansia (ß = - 0.008, P = 7.60 × 10-3), F_Acidaminococcaceae (ß = 0.008, P = 1.22 × 10-2), G_Holdemanella (ß = - 0.007, P = 1.39 × 10-2) and O_Lactobacillales (ß = 0.006, P = 1.79× 10-2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (ß = 0.010, P = 4.00× 10-4), O_Selenomonadales (ß = - 0.010, P = 1.20 × 10-3), O_Clostridiales (ß = 0.009, P = 2.70 × 10-3) and G_Holdemanella (ß = - 0.008, P = 4.20 × 10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.
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Trastornos de Ansiedad/microbiología , Eje Cerebro-Intestino , Proteína C-Reactiva/fisiología , Trastorno Depresivo/microbiología , Disbiosis/microbiología , Microbioma Gastrointestinal/fisiología , Genes Bacterianos , Adulto , Anciano , Trastornos de Ansiedad/etiología , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/fisiopatología , Bacterias/genética , Bacterias/aislamiento & purificación , Trastorno Depresivo/etiología , Trastorno Depresivo/genética , Trastorno Depresivo/fisiopatología , Disbiosis/genética , Disbiosis/fisiopatología , Femenino , Fermentación , Microbioma Gastrointestinal/genética , Estudio de Asociación del Genoma Completo , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Riesgo , Índice de Severidad de la Enfermedad , Especificidad de la Especie , Encuestas y CuestionariosRESUMEN
Recent animal studies have supported that Lactobacillus plantarum PS128 (PS128) can reduce the severity of anxiety and depression. However, previous studies did not focus on the sleep quality and mood of humans. This study determines whether PS128 reduces the severity of anxiety and depressive symptoms, regulates autonomic nervous system function, and improves sleep quality. Forty participants between 20 and 40 years of age with self-reported insomnia were randomly assigned to two groups, a PS128 group and a placebo group, in a double-blind trial. Participants took two capsules of either PS128 or a placebo after dinner for 30 days. Study measures included subjective depressive symptoms, anxiety and sleep questionnaires, and miniature-polysomnography recordings at baseline and on the 15th and 30th days of taking capsules. Overall, all outcomes were comparable between the two groups at baseline and within the 30-day period, yet some differences were still found. Compared to the control group, the PS128 group showed significant decreases in Beck Depression Inventory-II scores, fatigue levels, brainwave activity, and awakenings during the deep sleep stage. Their improved depressive symptoms were related to changes in brain waves and sleep maintenance. These findings suggest that daily administration of PS128 may lead to a decrease in depressive symptoms, fatigue level, cortical excitation, and an improvement in sleep quality during the deep sleep stage. Daily consumption of PS128 as a dietary supplement may improve the depressive symptoms and sleep quality of insomniacs, although further investigation is warranted.
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Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Lactobacillus plantarum , Probióticos , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Sueño , Adulto , Afecto , Ansiedad/complicaciones , Ansiedad/microbiología , Trastornos de Ansiedad/complicaciones , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/microbiología , Ondas Encefálicas , Depresión/complicaciones , Depresión/microbiología , Trastorno Depresivo/complicaciones , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/microbiología , Método Doble Ciego , Fatiga , Femenino , Microbioma Gastrointestinal , Humanos , Masculino , Proyectos Piloto , Polisomnografía , Pruebas Psicológicas , Autoinforme , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Trastornos del Inicio y del Mantenimiento del Sueño/microbiología , Fases del SueñoRESUMEN
Understanding how the microbiome influences health and disease has emerged as an important area of research across all domains of biomedical and health sciences. An extensive body of work in animal models has established a link between the gut microbiome and anxiety-like behaviour. Foundational work on germ-free mice provided the catalyst for neuroscientists to consider the microbiota-brain axis and brain health. Research manipulating the microbiome, including use of germ-free mice, antibiotics, and probiotics, provide evidence that the microbiota influences stress systems and in particular anxiety-like behaviour. Consideration of anxiety-like behaviour in animal models of metabolic and inflammatory disorders expands the scope of the work and correlates in clinical studies are emerging. This chapter highlights the work done to date in animal studies and reviews the recent clinical literature translating these observations to anxiety disorders.
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Trastornos de Ansiedad , Ansiedad , Encéfalo , Microbioma Gastrointestinal/fisiología , Animales , Ansiedad/inmunología , Ansiedad/metabolismo , Ansiedad/microbiología , Trastornos de Ansiedad/inmunología , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/microbiología , Encéfalo/microbiología , Encéfalo/fisiología , Humanos , PsicofisiologíaRESUMEN
Anxiety and eating disorders produce a physiological imbalance that triggers alterations in the abundance and composition of gut microbiota. Moreover, the gut-brain axis can be altered by several factors such as diet, lifestyle, infections, and antibiotic treatment. Diet alterations generate gut dysbiosis, which affects immune system responses, inflammation mechanisms, the intestinal permeability, as well as the production of short chain fatty acids and neurotransmitters by gut microbiota, which are essential to the correct function of neurological processes. Recent studies indicated that patients with generalized anxiety or eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorders) show a specific profile of gut microbiota, and this imbalance can be partially restored after a single or multi-strain probiotic supplementation. Following the PRISMA methodology, the current review addresses the main microbial signatures observed in patients with generalized anxiety and/or eating disorders as well as the importance of probiotics as a preventive or a therapeutic tool in these pathologies.
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Trastornos de Ansiedad/microbiología , Ansiedad/microbiología , Trastornos de Alimentación y de la Ingestión de Alimentos/microbiología , Probióticos/uso terapéutico , Animales , Ansiedad/terapia , Trastornos de Ansiedad/terapia , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Microbioma Gastrointestinal , HumanosRESUMEN
BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities. METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions. KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745. CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.
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Trastornos de Ansiedad/microbiología , Encéfalo , Trastorno Depresivo/microbiología , Microbioma Gastrointestinal , Síndrome del Colon Irritable/microbiología , Trastornos de Ansiedad/psicología , Trastorno Depresivo/psicología , Humanos , Síndrome del Colon Irritable/psicologíaRESUMEN
RATIONALE: Methamphetamine is a highly abused psychostimulant drug and its use remains a major public health concern worldwide with limited effective treatment options. Accumulative evidence reveals the influence of gut microbiota on the brain, behavior, and health as a part of the gut-brain axis but its involvement in modulating this substance use disorder remains poorly understood. OBJECTIVE: We sought to determine whether methamphetamine exposure and cessation or withdrawal alter the intestinal gut microbiota as well as characterize cessation-induced behavioral changes. METHODS: Male, Sprague-Dawley rats were administered methamphetamine (2 mg/kg; s.c.) or vehicle (n = 8 per group) twice per day for 14 consecutive days. On various days before, during, and after administration, fecal samples were collected and tests of anxiety- and depressive-like behaviors were conducted. RESULTS: Methamphetamine administration and cessation did not alter the relative abundance of bacteria but significantly changed the composition of gut bacteria through 16S rRNA sequencing. These changes were normalized after 7 days of methamphetamine cessation. Moreover, acute methamphetamine cessation induced depressive-like behavior, with an increase in immobility in the forced swim test but did not alter anxiety-like behaviors in tests of open field test or elevated plus maze. CONCLUSIONS: These findings provide direct evidence that methamphetamine and its cessation cause gut dysbiosis and that the latter associates with depressive-like behavior in rodents. Our observation will contribute to a better understanding of the function of gut microbiota in the process of substance use disorders and guide the choice of target therapeutics.
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Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Metanfetamina/toxicidad , Animales , Ansiedad/microbiología , Trastornos de Ansiedad/inducido químicamente , Trastornos de Ansiedad/microbiología , Encéfalo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Depresión/inducido químicamente , Depresión/microbiología , Relación Dosis-Respuesta a Droga , Disbiosis/microbiología , Heces/microbiología , Masculino , Metanfetamina/administración & dosificación , ARN Ribosómico 16S/genética , Ratas , Ratas Sprague-Dawley , NataciónRESUMEN
BACKGROUND: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. METHOD: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. RESULTS: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively). CONCLUSION: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.
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Ansiolíticos/farmacología , Antidepresivos/farmacología , Antipsicóticos/farmacología , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/microbiología , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Adulto , Anciano , Ansiolíticos/efectos adversos , Antidepresivos/efectos adversos , Antipsicóticos/efectos adversos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , ARN Ribosómico 16SRESUMEN
Anxiety disorders are the most prevalent mental health disorder worldwide, with a lifetime prevalence of 5-7 % of the human population. Although the etiology of anxiety disorders is incompletely understood, one aspect of host health that affects anxiety disorders is the gut-brain axis. Adolescence is a key developmental window in which stress and anxiety disorders are a major health concern. We used adolescent female mice in a gastrointestinal (GI) colonization model to demonstrate that the commensal fungus Candida albicans affects host health via the gut-brain axis. In mice, bacterial members of the gut microbiota can influence the host gut-brain axis, affecting anxiety-like behavior and the hypothalamus-pituitary-adrenal (HPA) axis which produces the stress hormone corticosterone (CORT). Here we showed that mice colonized with C. albicans demonstrated increased anxiety-like behavior and increased basal production of CORT as well as dysregulation of CORT production following acute stress. The HPA axis and anxiety-like behavior are negatively regulated by the endocannabinoid N-arachidonoylethanolamide (AEA). We demonstrated that C. albicans-colonized mice exhibited changes in the endocannabinoidome. Further, increasing AEA levels using the well-characterized fatty acid amide hydrolase (FAAH) inhibitor URB597 was sufficient to reverse both neuroendocrine phenotypes in C. albicans-colonized mice. Thus, a commensal fungus that is a common colonizer of humans had widespread effects on the physiology of its host. To our knowledge, this is the first report of microbial manipulation of the endocannabinoid (eCB) system that resulted in neuroendocrine changes contributing to anxiety-like behavior.
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Candida albicans/patogenicidad , Endocannabinoides/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Ansiedad/metabolismo , Ansiedad/microbiología , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/microbiología , Ácidos Araquidónicos/metabolismo , Encéfalo/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida albicans/metabolismo , Corticosterona/análisis , Corticosterona/sangre , Endocannabinoides/farmacología , Femenino , Sistema Hipotálamo-Hipofisario/fisiología , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Sistemas Neurosecretores/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/fisiología , Alcamidas Poliinsaturadas/metabolismo , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/metabolismo , Estrés Psicológico/microbiologíaRESUMEN
Mental disorders including depression and anxiety are often comorbid with gut problems, suggesting a bidirectional relationship between mental health and gut function. Several mechanisms might explain this comorbidity, such as inflammation and immune activation; intestinal permeability; perturbations in the hypothalamic-pituitary-adrenal axis; neurotransmitter/neuropeptide dysregulation; dietary deficiencies; and disturbed gut microbiome composition. The potential of modulating the microbiome-gut-brain axis, and subsequently mental health, through the use of functional foods, is an emerging and novel topic of interest. Fermented foods are considered functional foods due to their putative health benefits. The process of microbial fermentation converts food substrates into more nutritionally and functionally rich products, resulting in functional microorganisms (probiotics), substrates that enhance proliferation of beneficial bacteria in the gut (prebiotics), and bioactive components (biogenics). These functional ingredients act biologically in the gastrointestinal tract and have the ability to modify the gut microbiota, influence translocation of endotoxins and subsequent immune activation, and promote host nutrition. This narrative review explores the theoretical potential of the functional components present in fermented foods to alter gut physiology and to impact the biological mechanisms thought to underpin depression and anxiety. Pre-clinical studies indicate the benefits of fermented foods in relieving perturbed gut function and for animal models of depression and anxiety. However, in humans, the literature relating to the relevance of fermented food for treating or preventing depression and anxiety is sparse, heterogeneous and has significant limitations. This review identifies a critical research gap for further evaluation of fermented foods in the management of depression anxiety in humans.
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Trastornos de Ansiedad/dietoterapia , Trastorno Depresivo/dietoterapia , Alimentos Fermentados , Tracto Gastrointestinal/fisiología , Salud Mental , Animales , Trastornos de Ansiedad/microbiología , Trastorno Depresivo/microbiología , Alimentos Fermentados/microbiología , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Humanos , Inflamación/microbiología , Inflamación/fisiopatologíaRESUMEN
BACKGROUND: Associations between abnormal gut microbiome compositions and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome composition is associated with the severity of generalized anxiety disorder (GAD) and relief from clinical symptoms in patients. METHODS: Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 month after drug treatment. RESULTS: Gut microbiome compositions were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated negatively with the anxiety severity and positively with anxiety reduction, whereas the abundances of Bacteroides and Escherichia-Shigella were positively associated with anxiety severity. Sex, smoking, and alcohol intake influenced the gut microbiome composition. LIMITATIONS: The sample sizes were small and the stool samples were collected only at baseline; therefore, a causal association between changes in intestinal flora and disease remission was not established. Moreover, the effects of different drugs on gut microbiome composition were not investigated. CONCLUSIONS: Altered gut microbiome composition may contribute to GAD pathogenesis and remission.
Asunto(s)
Trastornos de Ansiedad/microbiología , Heces/microbiología , Microbiota , ARN Ribosómico 16S/análisis , Adulto , Femenino , Microbioma Gastrointestinal , Humanos , MasculinoRESUMEN
Converging evidence supports the involvement of pro-inflammatory pathways and the gut microbiome in major depressive disorder (MDD). Pre-clinical and clinical studies suggest that decreasing pro-inflammatory signaling may provide clinical benefit in MDD. In this study, we used the chronic unpredictable stress (CUS) paradigm to assess whether mice lacking the pro-inflammatory caspase 1, interferon gamma-receptor, and nitric oxide synthase (Casp1, Ifngr, Nos2)-/- present altered depressive- and anxiety-like behaviour at baseline and in response to CUS. In comparison to wild-type (wt) mice, (Casp1, Ifngr, Nos2)-/- mice displayed decreased depressive- and anxiety-like behaviour, and increased hedonic-like behaviour and locomotor activity at baseline, and resistance to developing anhedonic-like behaviour and a heightened emotional state following stress. Plasma levels of ACTH and CORT did not differ between the triple knockout and wt mice following stress. The faecal microbiome of (Casp1, Ifngr, Nos2)-/- mice differed from that of wt mice at baseline and displayed reduced changes in response to chronic stress. Our results demonstrate that simultaneous deficit in multiple pro-inflammatory pathways has antidepressant-like effects at baseline, and confers resilience to stress-induced anhedonic-like behaviour. Moreover, accompanying changes in the gut microbiome composition suggest that CASP1, IFNGR and NOS2 play a role in maintaining microbiome homeostasis.
Asunto(s)
Trastornos de Ansiedad , Conducta Animal , Caspasa 1/deficiencia , Trastorno Depresivo Mayor , Microbioma Gastrointestinal , Óxido Nítrico Sintasa de Tipo II/deficiencia , Receptores de Interferón/deficiencia , Animales , Trastornos de Ansiedad/genética , Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/fisiopatología , Caspasa 1/metabolismo , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/microbiología , Trastorno Depresivo Mayor/fisiopatología , Ratones , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores de Interferón/metabolismo , Receptor de Interferón gammaRESUMEN
INTRO: There has been an increased interest in understanding the therapeutic effect of gut-microbiota on health, particularly in mental health. However, limited research into the connection between gut-microbiota and mental health makes this study an important endeavor in exploring the effect of gut-microbiota, through probiotics intervention, on mental health like anxiety and factors related to anxiety (e.g., anxiety control, affect, negative mood regulation, and worry). METHOD: Healthy college students (N = 86; 75.6% female), average age of 20.59, participated in a double-blind, placebo-control, and randomization-control study. Eligible participants completed a baseline survey before being assigned to a condition, which consisted of four probiotics conditions and one placebo condition. After 28 days of daily intake, the participants returned to complete their exit survey. RESULT: Probiotics were observed to improve panic anxiety, neurophysiological anxiety, negative affect, worry, and increase negative mood regulation. Furthermore, post hoc analyses revealed that the CFU (colony-forming unit) level was more effective than species counts in accounting for the number of significant improvements. A ceiling effect was detected in the study, participants with high distress reported higher number of improvements than those with normative distress. CONCLUSION: Overall, this study is the first to examine the effect of CFU and species count on probiotics' efficacy. The study's finding suggested that probiotics may have the therapeutic potential to treat anxiety, however, further research is necessary to make that determination.
Asunto(s)
Trastornos de Ansiedad/microbiología , Trastornos de Ansiedad/terapia , Encéfalo/microbiología , Microbioma Gastrointestinal , Probióticos/uso terapéutico , Afecto/fisiología , Método Doble Ciego , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Our current understanding of the underlying mechanisms and etiologies of perinatal mood and anxiety disorders (PMADs) is not clearly identified. The relationship of stress-induced adaptations (i.e., the hypothalamic-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS), the immune system) and the microbiota are potential contributors to psychopathology exhibited in women during pregnancy and postpartum and should be investigated. RECENT FINDINGS: The stress response activates the HPA axis and dysregulates the ANS, leading to the inhibition of the parasympathetic system. Sustained high levels of cortisol, reduced heart variability, and modulated immune responses increase the vulnerability to PMAD. Bidirectional communication between the nervous system and the microbiota is an important factor to alter host homeostasis and development of PMAD. Future research in the relationship between the psychoneuroimmune system, the gut microbiota, and PMAD has the potential to be integrated in clinical practice to improve screening, diagnosis, and treatment.