Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

---

Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(4), P. 222 - 247

Published: Feb. 14, 2024

Crosstalk between gut and brain has long been appreciated in health disease, the microbiota is a key player communication these two distant organs. Yet, mechanisms through which influences development function of gut–brain axis remain largely unknown. Barriers present are specialized cellular interfaces that maintain strict homeostasis different compartments across this axis. These barriers include epithelial barrier, blood–brain barrier blood–cerebrospinal fluid barrier. ideally positioned to receive communicate microbial signals constituting gateway for gut–microbiota–brain communication. In Review, we focus on how modulation by can constitute an important channel Moreover, malfunction upon alterations composition could form basis various conditions, including often comorbid neurological gastrointestinal disorders. Thus, should unravelling molecular move from simplistic framing as 'leaky gut'. A mechanistic understanding barriers, especially during critical windows development, be aetiology The modulator This Review provides overview examines role disease.

Language: Английский

---

Anti-Inflammatory, Antioxidant, and Neuroprotective Effects of Polyphenols—Polyphenols as an Element of Diet Therapy in Depressive Disorders

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2258 - 2258

Published: Jan. 23, 2023

Depressive disorders can affect up to 350 million people worldwide, and in developed countries, the percentage of patients with depressive may be as high 10%. During depression, activation pro-inflammatory pathways, mitochondrial dysfunction, increased markers oxidative stress, a reduction antioxidant effectiveness body are observed. It is estimated that approximately 30% depressed do not respond traditional pharmacological treatments. However, more attention being paid influence active ingredients food on course risk neurological disorders, including depression. The possibility using foods containing polyphenols an element diet therapy depression was analyzed review. whether consumption products such could alleviate or prevent progression it also considered. Results from preclinical studies demonstrate potential phenolic compounds have reduce behaviors by regulating factors related neuroinflammation, modulation intestinal microbiota.

Language: Английский

---

Balancing the Mind: Toward a Complete Picture of the Interplay between Gut Microbiota, Inflammation and Major Depressive Disorder

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 216, P. 111056 - 111056

Published: Aug. 24, 2024

The intricate interplay existing between gut microbiota and homeostasis extends to the realm of brain, where emerging research underscores significant impact on mood regulation overall neurological well-being vice-versa, with inflammation playing a pivotal role in mediating these complex interactions. This comprehensive review explores inflammation, alterations microbiota, their major depressive disorder (MDD). It provides cohesive framework for puzzle pieces this triad, emphasizing recent advancements understanding inflammatory states' contribution features. Two directions communication brain depression are discussed, serving as potential modulator. Therapeutic implications were discussed well, drawing insights from interventional studies effects probiotics bacterial composition symptoms. Ultimately, will attempt provide complete valuable future therapeutic interventions MDD.

Language: Английский

---

Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia

Gut, Journal Year: 2024, Volume and Issue: 73(10), P. 1749 - 1762

Published: June 8, 2024

Mounting evidence underscores the pivotal role of intestinal barrier and its convoluted network with diet microbiome in pathogenesis inflammatory bowel disease (IBD) colitis-associated colorectal cancer (CRC). Moreover, bidirectional association liver brain, known as gut-brain axis, plays a crucial developing complications, including extraintestinal manifestations IBD CRC metastasis. Consequently, healing represents therapeutic target these inflammatory-dependent disorders, assessment predicting outcomes, response to therapy manifestations.New advanced technologies are revolutionising our understanding paradigm, enabling accurate aiding unravelling complexity axis. Cutting-edge endoscopic imaging techniques, such ultra-high magnification endocytoscopy probe-based confocal laser endomicroscopy, new allowing real-time exploration 'cellular' barrier. Additionally, novel spatial technology platforms, multispectral imaging, upconversion nanoparticles, digital profiling, optical spectroscopy mass cytometry, enable deep comprehensive 'molecular' 'ultrastructural' In this promising landscape, artificial intelligence standardising integrating tools, thereby contributing prediction outcomes.Looking ahead, integrated approach holds promise uncovering targets, breaking ceiling IBD. Novel molecules, dietary interventions modulation strategies aim restore, reinforce, or modulate These advancements have potential for transformative personalised approaches managing

Language: Английский

---

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

---

Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats

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

Published: March 26, 2024

Quercetin, an abundant flavonoid compound in plants, is considered a novel antidepressant; however, its mechanisms of action are poorly understood. This study aimed to investigate the therapeutic effects quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors rats and explore underlying by combining untargeted metabolomics 16S rRNA sequencing analysis brain tissue metabolites gut microbiota. Gut microbiota revealed that at phylum level, reduced Firmicutes Firmicutes/Bacteroidetes (F/B) ratio enhanced Cyanobacteria . At genus downregulated 6 upregulated 14 bacterial species. Metabolomics regulated multiple metabolic pathways, including glycolysis/gluconeogenesis, sphingolipid metabolism, pentose phosphate pathway, coenzyme A biosynthesis. modulation leads improvements phenotypes, anxiety-like cognitive function, highlighting potential treating depression.

Language: Английский

---

The gut microbiota–brain axis in neurological disorders

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 20, 2024

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as microbiota–gut–brain axis (MGBA). The MGBA influences host's nervous system development, emotional regulation, cognitive function through neurotransmitters, immune modulation, metabolic pathways. Factors like diet, lifestyle, genetics, environment shape composition together. Most research explored how regulates host physiology its potential in preventing treating neurological disorders. However, individual heterogeneity of microbiota, strains playing dominant role diseases, interactions these microbial metabolites with central/peripheral systems still need exploration. This review summarizes driving neurodevelopmental disorders (autism spectrum disorder attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's Parkinson's disease), mood (anxiety depression) recent years discusses current clinical preclinical microbe‐based interventions, including dietary intervention, probiotics, prebiotics, fecal transplantation. It also puts forward insufficient on provides framework for further

Language: Английский

---

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Biological Research, Journal Year: 2024, Volume and Issue: 57(1)

Published: May 6, 2024

Abstract Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest role microbiome-gut-brain axis signaling, including for brain serotonergic systems relationship between HFD anxiety. Evidence suggests gut microbiome system together may play an important this response. Here we conducted nine-week protocol male rats, followed by analysis diversity community composition, brainstem gene expression ( tph2 , htr1a slc6a4 ), anxiety-related defensive behavioral responses. We show that decreased alpha altered composition association obesity, increased mRNA expression, caudal part dorsomedial dorsal raphe nucleus (cDRD), subregion previously stress- responses, and, finally, The Firmicutes/Bacteroidetes ratio relative to control diet, as well higher abundances Blautia decreases Prevotella . found were subregions HFD, diet. Specific bacterial taxa cDRD. Thus, propose HFD-induced obesity is microbiome-gut-serotonergic leading responses rats.

Language: Английский

---

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

---