Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

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

Published: June 19, 2023

Cognitive function in humans depends on the complex and interplay between multiple body systems, including hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells has a genetic potential that exceeds of genome, plays crucial role this interplay. microbiota-gut-brain (MGB) axis is bidirectional signalling pathway operates through neural, endocrine, immune, metabolic pathways. One major neuroendocrine systems responding to stress HPA produces glucocorticoids such as cortisol corticosterone rodents. Appropriate concentrations are essential for normal neurodevelopment function, well cognitive processes learning memory, studies have shown microbes modulate throughout life. Stress can significantly impact MGB via other Animal research advanced our understanding these mechanisms pathways, leading paradigm shift conceptual thinking about influence microbiota health disease. Preclinical trials currently underway determine how animal models translate humans. In review article, we summarize current knowledge relationship axis, cognition, provide an overview main findings conclusions broad field.

Language: Английский

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Gut Microbiota Metabolites in Major Depressive Disorder—Deep Insights into Their Pathophysiological Role and Potential Translational Applications

Metabolites, Journal Year: 2022, Volume and Issue: 12(1), P. 50 - 50

Published: Jan. 8, 2022

The gut microbiota is a complex and dynamic ecosystem essential for the proper functioning of organism, affecting health disease status individuals. There continuous bidirectional communication between host, conforming to unique entity known as “holobiont”. Among these crosstalk mechanisms, synthesizes broad spectrum bioactive compounds or metabolites which exert pleiotropic effects on human organism. Many microbial can cross blood–brain barrier (BBB) have significant brain, playing key role in so-called microbiota-gut-brain axis. An altered (MGB) axis major characteristic many neuropsychiatric disorders, including depressive disorder (MDD). Significative differences eubiosis dysbiosis mental disorders like MDD with their different metabolite composition concentrations are being discussed. In present review, main (short-chain fatty acids -SCFAs-, bile acids, amino tryptophan -trp- derivatives, more), signaling pathways functions will be summarized explain part pathophysiology. Conclusions from promising translational approaches related metabolome addressed more depth discuss possible clinical value management patients.

Language: Английский

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Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases

Translational Neurodegeneration, Journal Year: 2022, Volume and Issue: 11(1)

Published: June 4, 2022

Abstract Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The process is mediated by numerous metabolic pathways, most which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, experimental clinical evidence suggesting their possible therapeutic use as disease-modifiers in diseases. Experimental on the mechanisms underlying TUDCA’s action derives from animal models Alzheimer’s disease, Parkinson’s Huntington’s diseases, amyotrophic lateral sclerosis (ALS) cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only regulating inhibiting apoptotic cascade, but also reducing oxidative stress, protecting mitochondria, producing an anti-neuroinflammatory action, acting a chemical chaperone maintain stability correct folding proteins. Furthermore, data phase II trials be safe potential disease-modifier ALS. ALS first disease being treated acids. While further accumulated for other stands promising treatment

Language: Английский

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Gut Microbiota, an Additional Hallmark of Human Aging and Neurodegeneration

Neuroscience, Journal Year: 2023, Volume and Issue: 518, P. 141 - 161

Published: March 7, 2023

Gut microbiota represents a diverse and dynamic population of microorganisms harbouring the gastrointestinal tract, which influences host health disease. Bacterial colonization tract begins at birth changes throughout life, with age being one conditioning factors for its vitality. Aging is also primary risk factor most neurodegenerative diseases. Among them, Alzheimeŕs disease (AD) probably where association state dysbiosis gut has been studied. In particular, intestinal microbial-derived metabolites have associated β-amyloid formation brain amyloid deposition, tau phosphorylation, as well neuroinflammation in AD patients. Moreover, it suggested that some oral bacteria increase developing AD. However, causal connections among microbiome, amyloid-tau interaction, neurodegeneration need to be addressed. This paper summarizes emerging evidence literature regarding link between microbiome focus on Taxonomic features microbial functional alterations biomarkers are main points reviewed. Data from clinical studies determinants particularly emphasized. Further, relationships age-dependent epigenetic other neurological disorders described. Together, all this suggests that, sense, can seen an additional hallmark human aging neurodegeneration.

Language: Английский

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Gut microbiota-driven metabolic alterations reveal gut–brain communication in Alzheimer’s disease model mice

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 23, 2024

The gut microbiota (GM) and its metabolites affect the host nervous system are involved in pathogeneses of various neurological diseases. However, specific GM alterations under pathogenetic pressure their contributions to "microbiota – metabolite brain axis" Alzheimer's disease (AD) remain unclear. Here, we investigated fecal, serum, cortical metabolomes APP/PS1 wild-type (WT) mice, revealing distinct hub bacteria AD mice within scale-free networks shared by both groups. Moreover, identified diverse peripheral central metabolic landscapes between WT that featured bile acids (e.g. deoxycholic isodeoxycholic acid) unsaturated fatty 11Z-eicosenoic palmitoleic acid). Machine-learning models revealed relationships differential/hub these signatures from periphery brain. Notably, AD-enriched Dubosiella affected occurrence via acid vice versa. Considering transgenic background propose enrichment impedes progression synthesis acid, which has protective properties against inflammation disorders. We another association involving fecal acid-mediated interactions Erysipelatoclostridium occurrence, was corroborated correlation deoxycholate levels cognitive scores humans. Overall, this study elucidated network alterations, landscapes, mediatory roles thus critical pathogenesis communications pressure.

Language: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

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The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

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Advances in dietary polyphenols: Regulation of inflammatory bowel disease (IBD) via bile acid metabolism and the gut-brain axis

Food Chemistry, Journal Year: 2025, Volume and Issue: 472, P. 142932 - 142932

Published: Jan. 21, 2025

Language: Английский

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Regulation of body weight: Lessons learned from bariatric surgery

Molecular Metabolism, Journal Year: 2022, Volume and Issue: 68, P. 101517 - 101517

Published: May 26, 2022

Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting pharmacology, its beneficial effects are sustained over decades in patients, mortality among lowest major surgery. Because there not nearly enough surgeons to implement bariatric on a global scale, intensive research efforts have begun identify mechanisms of action molecular level order replace with targeted behavioral pharmacological treatments. To date, however, no consensus as critical involved. The purpose this non-systematic review evaluate existing evidence specific inter-organ signaling pathways that play roles surgery-induced benefits, focus Roux-en-Y gastric bypass (RYGB) vertical sleeve gastrectomy (VSG), both humans rodents. Gut-brain communication brain targets food intake control energy balance regulation complex redundant. Although relatively young science has generated number hypotheses, clear unique mechanism yet emerged. It seems increasingly likely broad physiological produced by do involve single mechanism, but rather multiple pathways. Besides need improve better validate surgeries animals, advanced techniques, including inducible, tissue-specific knockout models, use humanized traits will be necessary. State-of-the-art genetically-guided neural identification techniques should used more selectively manipulate function-specific

Language: Английский

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Inflammatory Bowel Disease and Neurodegenerative Diseases

Gut and Liver, Journal Year: 2023, Volume and Issue: 17(4), P. 495 - 504

Published: Feb. 27, 2023

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci comorbidities IBD mood disorders.These new discoveries stem from improved understanding the gut-microbiome-brain axis: specifically, ability intestinal microbiota to modulate inflammation regulate neuromodulatory compounds.Clinical retrospective studies incorporating large sample sizes population-based cohorts have confirmed relevance chronic neurodegeneration in clinical medicine.In this review, we expound upon current knowledge on axis, highlighting several plausible mechanisms linking with neurodegeneration.We also summarize known associations Parkinson disease, Alzheimer vascular dementia ischemic stroke, multiple sclerosis a context.Finally, discuss implications axis preventing, diagnosing, managing among non-IBD patients.(

Language: Английский

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