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

---

Probiotics for Neurodegenerative Diseases: A Systemic Review

Microorganisms, Journal Year: 2023, Volume and Issue: 11(4), P. 1083 - 1083

Published: April 20, 2023

Neurodegenerative disorders (ND) are a group of conditions that affect the neurons in brain and spinal cord, leading to their degeneration eventually causing loss function affected areas. These can be caused by range factors, including genetics, environmental lifestyle choices. Major pathological signs these diseases protein misfolding, proteosomal dysfunction, aggregation, inadequate degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, fragmentation Golgi apparatus neurons, disruption axonal transport, dysfunction neurotrophins (NTFs), neuroinflammatory or neuroimmune processes, neurohumoral symptoms. According recent studies, defects imbalances gut microbiota directly lead neurological through gut-brain axis. Probiotics ND recommended prevent cognitive which is major symptom diseases. Many vivo clinical trials have revealed probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus casei, etc.) effective candidates against progression ND. It has been proven inflammatory process stress modulated modifying with help probiotics. As result, this study provides an overview available data, bacterial variety, axis defects, probiotics’ mode action averting A literature search on particular sites, PubMed, Nature, Springer Link, identified articles might pertinent subject. The contains following few groups terms: (1) OR (2) disorders. outcomes aid elucidating relationship between effects different neurodegenerative This systematic review will assist discovering new treatments future, as generally safe cause mild side some cases human body.

Language: Английский

---

The interplay between gut microbiota composition and dementia

Reviews in the Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Recently, researchers have been interested in the potential connection between gut microbiota composition and various neuropsychological disorders. Dementia significantly affects socioeconomics of families. Gut is considered as a probable factor its pathogenesis. Multiple bacterial metabolites such short-chain fatty acids, lipopolysaccharides, neurotransmitters that are responsible for incidence progression dementia can be produced by microbiota. Various species Bifidobacterium breve , Akkermansia muciniphila Streptococcus thermophilus Escherichia coli Blautia hydrogenotrophica etc. implicated pathogenesis dementia. great target imitating or inhibiting their an adjunctive therapy based on role Therefore, some diets prevent decelerate altering composition. Moreover, probiotics modulate increasing beneficial bacteria reducing detrimental species. These therapeutic modalities novel methods probably safe effective. They enhance efficacy traditional medications improve cognitive function.

Language: Английский

---

Gut Microbiota as a Modifier of Huntington’s Disease Pathogenesis

Journal of Huntington s Disease, Journal Year: 2024, Volume and Issue: 13(2), P. 133 - 147

Published: May 10, 2024

Huntingtin (HTT) protein is expressed in most cell lineages, and the toxicity of mutant HTT multiple organs may contribute to neurological psychiatric symptoms observed Huntington's disease (HD). The proteostasis neurotoxicity are influenced by intracellular milieu responses environmental signals. Recent research has highlighted a prominent role gut microbiota brain immune system development, aging, progression disorders. Several studies suggest that might disrupt homeostasis (known as dysbiosis) impact pathogenesis HD. Dysbiosis been HD patients, animal models it coincides with aggregation, abnormal behaviors, reduced lifespan. This review article aims highlight potential pathways within microbiota-gut-immune-central nervous (CNS) axis. Understanding functions Wild-Type (WT) these associated networks elucidate novel pathogenic pathways, identify biomarkers peripheral therapeutic targets for

Language: Английский

---

What the Gut Tells the Brain—Is There a Link between Microbiota and Huntington’s Disease?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4477 - 4477

Published: Feb. 24, 2023

The human intestinal microbiota is a diverse and dynamic microenvironment that forms complex, bi-directional relationship with the host. microbiome takes part in digestion of food generation crucial nutrients such as short chain fatty acids (SCFA), but also impacts host's metabolism, immune system, even brain functions. Due to its indispensable role, has been implicated both maintenance health pathogenesis many diseases. Dysbiosis gut already neurodegenerative diseases Parkinson's disease (PD) Alzheimer's (AD). However, not much known about composition interactions Huntington's (HD). This dominantly heritable, incurable caused by expansion CAG trinucleotide repeats huntingtin gene (HTT). As result, toxic RNA mutant protein (mHTT), rich polyglutamine (polyQ), accumulate particularly brain, leading impaired Interestingly, recent studies indicated mHTT widely expressed intestines could possibly interact microbiota, affecting progression HD. Several have aimed so far screen mouse models HD find out whether observed dysbiosis affect functions brain. review summarizes ongoing research field highlights essential role intestine-brain axis progression. puts strong emphasis on indicating future target urgently needed therapy for this still disease.

Language: Английский

---

Circadian Interventions in Preclinical Models of Huntington’s Disease: A Narrative Review

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1777 - 1777

Published: Aug. 6, 2024

Huntington's Disease (HD) is a neurodegenerative disorder caused by an autosomal-dominant mutation in the huntingtin gene, which manifests with triad of motor, cognitive and psychiatric declines. Individuals HD often present disturbed sleep/wake cycles, but it still debated whether altered circadian rhythms are intrinsic to its aetiopathology or consequence. Conversely, well established that disturbances, perhaps acting concert other pathophysiological mechanisms, worsen impact disease on motor functions burden patients their caretakers. Currently, there no cure stop progression HD, however, preclinical research providing cementing evidence restoring fluctuation can assist delaying onset slowing HD. Here we highlight application circadian-based interventions models provide insights into potential translation clinical practice. Interventions aimed at improving cycles' synchronization have shown improve deficits models. Therefore, strong support for suitability ameliorate symptoms humans emerges from literature, albeit gaps our knowledge underlying mechanisms possible risks associated implementation.

Language: Английский

---

Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

SUMMARY The native microbiome influences a plethora of host processes, including neurological function. However, its impacts on diverse brain cell types remains poorly understood. Here, we performed single nucleus RNA sequencing hippocampi from wildtype, germ-free mice and reveal the microbiome-dependent transcriptional landscape across all major neural types. We found conserved key adaptive immune neurodegenerative pathways, underscoring microbiome’s contributions to disease-relevant processes. Mono-colonization with select indigenous microbes identified species-specific effects state myeloid cells. Colonization by Escherichia coli induced distinct neurogenerative disease-associated state, suggesting increased disease susceptibility. Indeed, E. exposure in 5xFAD mouse model resulted exacerbated cognitive decline amyloid pathology, demonstrating sufficiency worsen Alzheimer’s outcomes. Together, these results emphasize broad, species-specific, consequences highlight capacity specific modulate Highlights Discrete specifically resident status. Gut triggers dynamic responses Exposure exacerbates behavioral cellular pathologies mice.

Language: Английский

---

Paradigms and Success Stories of Natural Products in Drug Discovery Against Neurodegenerative Disorders (NDDs)

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 22(6), P. 992 - 1015

Published: Jan. 6, 2023

Neurodegenerative disorders (NDDs) are multifaceted complex that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented challenge in drug discovery continuous efforts progress search suitable therapeutic candidates. Nature wealth active principles its lap cured human population since ancient times. Natural products revealed several benefits over conventional synthetic medications scientists shifted their vision towards exploring potentials natural past few years. structural mimicking compounds to endogenous ligands them as potential candidate prevent development NDDs. In review, authors summarized demographical facts about various including Alzheimer's disease (AD), Parkinson's (PD), Huntington's (HD) types sclerosis brain. significant findings new origin along with on been included. Also, description clinical trials patents enlisted this compilation. Although shown promising success against NDDs, still use is associated ethical issues which need be solved upcoming time.

Language: Английский

---

Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease

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

Published: Nov. 3, 2022

Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate symptoms delay progression BACHD mouse model of HD. Adult WT male mice were fed normal or ketogenic (KD) 3 months. The KD evoked robust rhythm serum levels β-hydroxybutyrate dramatic changes microbiome mice. NanoString analysis revealed transcriptional driven by striatum both have been reported models HD patients. Having established that had effects on mutant mice, examined its impact cycles. increased daytime sleep improved timing onset, while other parameters not altered. addition, activity rhythms, rhythmic power, reduced inappropriate onset variability. Importantly, motor performance rotarod challenging beam tests. It is worth emphasizing genetically caused no known cure. Life-style only improve quality life but also greatly needed. Our study demonstrates therapeutic potential diet-based treatment strategies pre-clinical

Language: Английский

---

Brain–Periphery Interactions in Huntington’s Disease: Mediators and Lifestyle Interventions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4696 - 4696

Published: April 25, 2024

Prominent pathological features of Huntington’s disease (HD) are aggregations mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea dystonia) non-motor symptoms. However, numerous systemic peripheral deficits HD have gained increasing attention recently, since those factors likely modulate progression, including pathology. While whole-body metabolic abnormalities organ-specific pathologies been relatively well described, potential mediators compromised inter-organ communication insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation inflammatory factors, circulating mHtt, many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired communication, gut–brain muscle–brain axis. Based on these findings, aimed assess risks potentials lifestyle interventions thought improve across axes: dietary strategies exercise. We conclude appropriate great reduce symptoms potentially modify progression (possibly via improving signaling) HD. metabolism warrant particular care design exercise programs for people with

Language: Английский

---