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

---

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

---

Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis

Brain, Journal Year: 2023, Volume and Issue: 146(12), P. 4916 - 4934

Published: Oct. 18, 2023

Alzheimer's disease is a complex neurodegenerative disorder leading to decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor by showing specific alterations microbiome composition of patients rodent models. However, it unknown whether are causal manifestation symptoms. To understand involvement patient host physiology behaviour, we transplanted faecal from age-matched healthy controls into microbiota-depleted young adult rats. We found impairments behaviours reliant on hippocampal neurogenesis, essential process for certain memory functions mood, resulting transplants. Notably, severity correlated with clinical scores donor patients. Discrete changes rat caecal metabolome were also evident. As neurogenesis cannot be measured living humans but modulated circulatory systemic environment, assessed impact environment proxy readouts. Serum decreased human cells vitro associated key microbial genera. Our findings reveal first time, that symptoms can transferred organism via microbiota, confirming role disease, highlight converging central cellular regulating gut-mediated factors Alzheimer's.

Language: Английский

---

Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Dec. 13, 2022

Vitamin B consists of a group water-soluble micronutrients that are mainly derived from the daily diet. They serve as cofactors, mediating multiple metabolic pathways in humans. As an integrated part human health, gut microbiota could produce, consume, and even compete for vitamin with host. The interplay between host might be crucial factor affecting absorbing processes B. On other hand, supplementation or deficiency impact growth specific bacteria, resulting changes composition function microbiota. Together, systemically contribute to health. In this review, we summarized interactions tried reveal underlying mechanism so can have better understanding its role

Language: Английский

---

Current understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies

Experimental & Molecular Medicine, Journal Year: 2024, Volume and Issue: 56(1), P. 86 - 94

Published: Jan. 4, 2024

Abstract Alzheimer’s disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of not completely clear. Recently, anti-Aβ antibodies have been shown remove amyloid from brain and slow clinical progression mild dementia by ~30%. However, exploring alternative strategies crucial understanding developing more effective therapeutic interventions. In recent years, microbiota-gut-brain axis has received significant attention in AD field. Numerous studies suggested that alterations gut microbiota composition are associated with AD, several underlying mechanisms proposed. area still their infancy, many aspects field just beginning be explored understood. Gaining deeper intricate interactions signaling pathways involved microbiota-AD interaction for optimizing targeting positively impact AD. review, we aim summarize current We will discuss existing evidence regarding role pathogenesis, mechanisms, biological factors influencing microbiome-gut-brain remaining questions Last, potential approaches recondition community alleviate progression. An ongoing exploration gut-brain development microbiota-based therapies hold advancing management future.

Language: Английский

---

The changing metabolic landscape of bile acids – keys to metabolism and immune regulation

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(7), P. 493 - 516

Published: April 4, 2024

Language: Английский

---

Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 29, 2024

Abstract Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut play a role in anabolic resistance of older muscle, cognition. In this placebo controlled double blinded randomised trial 36 twin pairs (72 individuals), aged ≥60, each pair are block to receive either or prebiotic daily for 12 weeks. Resistance exercise branched chain amino acid (BCAA) supplementation is prescribed all participants. Outcomes physical function The carried out remotely using video visits, online questionnaires testing, posting equipment biological samples. supplement well tolerated results changed microbiome [e.g., increased relative Bifidobacterium abundance]. There no significant difference between the primary outcome chair rise time (β = 0.579; 95% CI −1.080-2.239 p 0.494). improves cognition (factor score versus −0.482; CI,−0.813, −0.141; 0.014)). Our demonstrate cheap readily available interventions improve our ageing population. We illustrate feasibility delivered trials people, which could reduce under-representation people clinical trials. ClinicalTrials.gov registration: NCT04309292.

Language: Английский

---

Assessing the contribution of the chemical exposome to neurodegenerative disease

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 812 - 821

Published: April 29, 2024

Language: Английский

---

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

---

The Brain–Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4130 - 4130

Published: July 15, 2024

Neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s (PD), are severe age-related disorders with complex multifactorial causes. Recent research suggests a critical link between neurodegeneration the gut microbiome, via gut–brain communication pathway. This review examines role of trimethylamine N-oxide (TMAO), microbiota-derived metabolite, in development AD PD, investigates its interaction microRNAs (miRNAs) along this bidirectional TMAO, which is produced from dietary metabolites like choline carnitine, has been linked to increased neuroinflammation, protein misfolding, cognitive decline. In AD, elevated TMAO levels associated amyloid-beta tau pathologies, blood–brain barrier disruption, neuronal death. can cross promote aggregation amyloid proteins. Similarly, affects alpha-synuclein conformation aggregation, hallmark PD. also activates pro-inflammatory pathways NF-kB signaling, exacerbating neuroinflammation further. Moreover, modulates expression various miRNAs that involved neurodegenerative processes. Thus, microbiome–miRNA–brain axis represents newly discovered mechanistic dysbiosis neurodegeneration. MiRNAs regulate key oxidative stress, death, contributing progression. As direct consequence, specific miRNA signatures may serve potential biomarkers for early detection monitoring PD aims elucidate interrelationships microbiota, trimethylamine-N-oxide (miRNAs), central nervous system, implications these connections diseases. context, an overview current neuroradiology techniques available studying animal models used investigate intricate pathologies will be provided. summary, bulk evidence supports concept modulating pathway through changes, manipulation and/or miRNA-based therapies offer novel approaches implementing treatment debilitating neurological disorders.

Language: Английский

---