The brain-gut-microbiota interplay in depression: A key to design innovative therapeutic approaches

Pharmacological Research, Journal Year: 2023, Volume and Issue: 192, P. 106799 - 106799

Published: May 19, 2023

Depression is the most prevalent mental disorder in world associated with huge socio-economic consequences. While depressive-related symptoms are well known, molecular mechanisms underlying disease pathophysiology and progression remain largely unknown. The gut microbiota (GM) emerging as a key regulator of central nervous system homeostasis by exerting fundamental immune metabolic functions. In turn, brain influences intestinal microbial composition through neuroendocrine signals, within so-called microbiota-brain axis. balance this bidirectional crosstalk important to ensure neurogenesis, preserve integrity blood-brain barrier avoid neuroinflammation. Conversely, dysbiosis permeability negatively affect development, behavior, cognition. Furthermore, although not fully defined yet, changes GM depressed patients reported influence pharmacokinetics common antidepressants affecting their absorption, metabolism, activity. Similarly, neuropsychiatric drugs may shape turn an impact on efficacy toxicity pharmacological intervention itself. Consequently, strategies aimed at re-establishing correct homeostatic (i.e., prebiotics, probiotics, fecal transplantation, dietary interventions) represent innovative approach improve pharmacotherapy depression. Among these, probiotics Mediterranean diet, alone or combination standard care, hold promise for clinical application. Therefore, disclosure intricate network between depression will give precious insights diagnostic therapeutic approaches towards depression, profound implications drug development practice.

Language: Английский

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The bidirectional interaction between antidepressants and the gut microbiota: are there implications for treatment response?

International Clinical Psychopharmacology, Journal Year: 2024, Volume and Issue: 40(1), P. 3 - 26

Published: Feb. 6, 2024

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition function, exploring microbiota's possible role in modulating treatment outcomes. Antidepressants exert an influence measures of microbial diversity. The most consistently reported differences were β-diversity those exposed to antidepressants not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations users include increase Bacteroidetes phylum, Christensenellaceae family, Bacteroides Clostridium genera, while decrease was found Firmicutes Ruminococcaceae Ruminococcus genus. In addition, attenuate depressed healthy individuals, modulate serotonin transport, metabolic functions. These lyxose degradation, peptidoglycan maturation, membrane methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity abundance Roseburia Faecalibacterium are associated response, emerging as promising biomarkers. highlights for predictor response emphasizes need further research elucidate mechanisms underlying antidepressant-microbiota interactions. More homogeneous standardized techniques required confirm these initial findings.

Language: Английский

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Role of the gut–brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 189, P. 106348 - 106348

Published: Nov. 11, 2023

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated effects subdiaphragmatic vagotomy (SDV) modulating mice subjected chronic restrain (CRS). Pretreatment (10 mg/kg/day for 14 days) blocked anhedonia-like behavior reduced expression synaptic proteins brain-derived neurotrophic factor prefrontal cortex (PFC) CRS-exposed Interestingly, SDV beneficial on these alterations Analysis gut microbiome revealed four measures α-diversity between sham + CRS group group. Moreover, specific microbes differed vehicle group, differences microbial composition were observed all groups. Untargeted metabolomics analysis showed prevented increase plasma levels three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] positive correlations found two abundance several across In conclusion, our data suggest via vagus nerve might MDMA.

Language: Английский

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Stress-induced changes in cognitive function and intestinal barrier integrity can be ameliorated by venlafaxine and synbiotic supplementations

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e17033 - e17033

Published: Feb. 28, 2024

Stress profoundly impacts various aspects of both physical and psychological well-being. Our previous study demonstrated that venlafaxine (Vlx) synbiotic (Syn) treatment attenuated learned fear-like behavior recognition memory impairment in immobilized-stressed rats. In this study, we further investigated the physical, behavior, cellular mechanisms underlying effects Syn and/or Vlx on brain intestinal functions stressed Adult male Wistar rats, aged 8 weeks old were subjected to 14 days immobilization stress showed a decrease body weight gain food intake as well an increase water consumption, urinary corticosterone levels, adrenal gland weight. Supplementation rats resulted mitigation loss, restoration normal fluid intake, normalization levels. Behavioral analysis with enhanced depressive-like behaviors improved spatial learning-memory Hippocampal dentate gyrus stress-induced neuronal cell death, which was by treatment. Stress-induced ileum inflammation increased permeability effectively reduced supplementation Syn. addition, partly contributed affecting expression glial cell-derived neurotrophic factor hippocampus intestines suggesting particularly protective gut barrier brain. This highlights intricate interplay between physiological responses gut. intervention alleviate death modulate depression- impairment-like behaviors, improve dysfunction similar those Vlx. These findings enhance our understanding stress-related health conditions suggest may be promising approach ameliorate deleterious gut-brain axis.

Language: Английский

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Raspberry Ketone Prevents LPS‐Induced Depression‐Like Behaviors in Mice by Inhibiting TLR‐4/NF‐κB Signaling Pathway via the Gut‐Brain Axis

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: 68(11)

Published: May 17, 2024

Scope Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food‐derived phenolics. Raspberries, renowned globally their delectable flavor, harbor phenolic compound known as raspberry ketone (RK). However, impact RK on depressive symptoms remains ambiguous. This study aims to investigate lipopolysaccharide (LPS)‐induced depressed mice and elucidates its potential mechanisms, focusing gut‐brain axis. Methods results Through behavioral tests, exerts notable preventive effect LPS‐induced depression‐like behaviors in mice. proves capable attenuating gut inflammation, repairing barrier impairment, modulating composition microbiome ( Muribaculaceae , Streptococcus Lachnospiraceae Akkermansia ), promoting production short‐chain fatty acids. Furthermore, alleviates neuroinflammation by suppressing TLR‐4/NF‐κB pathway bolsters synaptic function elevating levels neurotrophic factors synapse‐associated proteins. Conclusion The current provides compelling evidence that effectively inhibits via axis, leading improvement addresses research gap understanding antidepressant effects illuminates utilizing functional food preventing depression.

Language: Английский

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Profiles of gut microbiota and metabolites for high risk of transgenerational depression‐like behavior by paternal methamphetamine exposure

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(3)

Published: Feb. 10, 2025

Abstract Parental substance abuse increases the risk of neurological and psychiatric disorders in offsprings. However, its underlying mechanism remains elusive. Our previous study demonstrated that long‐term exposure to methamphetamine (Meth), a psychostimulant drug with high addiction potential, remarkably alters gut microbiome metabolites male mice, which contribute Meth‐induced anxiety‐like behaviors. The current aimed investigate whether microbiota metabolism serve as potential peripheral targets for transgenerational mental problems by paternal Meth exposure. We found induced depression‐like behaviors both first (F1) second (F2) generations mice. Further, depletion bacteria through antibiotic treatments normalized normal levels F1 F2 Then, alterations bacterial composition were observed Specifically, Eubacterium_ruminantium_group, Enterorhabdus, Alloprevotella , Parabacteroides commonly affected taxa In addition, results showed LPC 14:1‐SN1 emerged consistently altered metabolite colons Taken together, our findings provide evidence enhances potentially mediated metabolism.

Language: Английский

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Exploring correlation between preoperative gut microbiota and PONV using 16S absolute quantitative sequencing: a prospective observational study

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 26, 2025

Background Postoperative nausea and vomiting (PONV) is a common complication following surgery. Despite various preventive measures, satisfactory outcomes have not been achieved. This study explores the potential of gut microbiota interactions with host in understanding preventing PONV, using 16S absolute quantitative sequencing technology to uncover new insights. Methods Patients who experienced within 24 h after surgery were divided into PONV group ( n = 22) non-PONV 22). Microbial communities linked assessed through bioinformatics analysis. Fecal samples from both groups transplanted rats, which then anesthetized isoflurane for 100 min. Pica behavior was monitored over next assess rats. Results Significant differences α - β -diversity observed between groups. Six key microorganisms identified, Bifidobacterium , Bilophila Oscillibacter showing negative correlation severity. Receiver operating characteristic (ROC) analysis demonstrated that could reliably predict PONV. Rats receiving feces exhibited significantly higher kaolin consumption post-anesthesia compared those group. Conclusion These results suggest mechanism involving microbiota, offering theoretical basis preoperative prediction based on microbial composition.

Language: Английский

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Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 24, 2023

Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with The mechanism by which Ziyan green ameliorates depression not clear.In this study, we examined impact on mice exhibiting symptoms similar to We specifically focused role intestinal and its metabolites. first established a chronic unpredictable mild stress (CUMS) mouse model induce depressive conducted behavioural tests, biochemical pathological tissue analysis. also investigated gut microbiota changes 16S rRNA sequencing measured faecal metabolites using UHPLC-MS/MS.The results showed that intervention improved depression-like behaviour, neurobiochemical factors, reduced levels pro-inflammatory factors CUMS mice. Spearman's correlation analysis different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) differential (Cholic acid, Deoxycholic etc.) depression-related indicators (5-HT, DA, BDNF, IL-6, TNF-α).In conclusion, our findings suggest both low high-dose interventions positive preventive effects without dose dependence, partly because they mainly affect Purine Metabolism, Bile Acid Biosynthesis Cysteine Metabolism mice, thus stimulating brain 5-HT, DA decreasing inflammatory TNF-α, activate composition flora, improve environment promote production metabolites, can be used for treatment. It suggested may achieve an antidepressant effect through gut-microbiota-brain axis.

Language: Английский

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The effects of venlafaxine on depressive-like behaviors and gut microbiome in cuprizone-treated mice

Frontiers in Psychiatry, Journal Year: 2024, Volume and Issue: 15

Published: June 3, 2024

Background Cuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on microbiome behavior CPZ-treated are largely unclear. Methods Male C57BL/6J were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce model demyelination. Meanwhile, microbiota behaviors assessed after with Ven (20 mg/kg/day) or equal volumes distilled water 2 by oral gavage from third week onward during CPZ treatment. Results treatment decreased sucrose preference rate in test increased immobility time tail-suspension test, it also induced an abnormality β-diversity changes microbial composition. alleviated regulated composition microbiota, such as increase Lactobacillus Bifidobacterium mice. Conclusion The anti-depressant might be related regulation

Language: Английский

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Faecal microbiota composition and impulsivity in a cohort of older adults with metabolic syndrome

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 14, 2024

Impulsivity is an important determinant of human behaviour, affecting self-control, reasonable thinking and food choices. Recent evidence suggests a role for gut microbiota in but the relationship between impulsive behaviours remains largely unexplored. To address this knowledge gap, present study aims to explore associations faecal composition with trait behavioural impulsivity, subcohort PREDIMED-Plus trial, including older adults presenting overweight/obesity. Fecal samples (n = 231) were profiled their using 16 S rRNA amplicon sequencing impulsivity was determined through four different assessments. Adherence dietary patterns estimated questionnaires. Beta diversity analyses showed significant association Conner's Performance Test (CPT) multivariate-adjusted models, and, total, 13 bacterial genera associated CPT. Erysipelotrichaceae UCG 003 highest CPT known butyrate producers such as Butyricicoccus spp., Roseburia Eubacterium hallii among identified bacteria. The bacteria Lachnospiraceae 001, Anaerostipes Blautia also adherence healthy unhealthy plant-based diets. In addition, functional analysis negative glucuronate galacturonate metabolic pathways. From other assessments, two more identified, genus Phascolarctobacterium Stroop test, GAG 54 positive urgency subscore UPPS-P Impulsive Behaviour Scale. Overall, our findings suggest potential links function inattention by

Language: Английский

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