Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(2)

Опубликована: Фев. 1, 2025

ABSTRACT Background A growing body of evidence suggests a link between the gut microbiota and Alzheimer's disease (AD), although underlying mechanisms remain elusive. This study aimed to investigate impact fecal transplantation (FMT) on cognitive function in mouse model AD. Methods Four‐month‐old 5 × FAD (familial disease) mice underwent antibiotic treatment deplete their native microbiota. Subsequently, they received FMT either weekly or every other day. After 8 weeks, β‐amyloid (Aβ) load were assessed through behavioral testing pathological analysis, respectively. The composition was analyzed using 16S rRNA sequencing. Results Initial failed alleviate memory deficits reduce brain Aβ pathology mice. In contrast, administered day effectively restored dysbiosis decreased lipopolysaccharide levels colon hippocampus. Mechanistically, reduced expression amyloid β precursor protein, β‐site APP cleaving enzyme 1, presenilin‐1, potentially by inhibiting Toll‐like receptor 4/inhibitor kappa B kinase β/nuclear factor kappa‐B signaling pathway. However, benefits diminished over time. Conclusion These findings demonstrate dose‐ time‐dependent efficacy mitigating AD‐like pathology, underscoring potential targeting for AD treatment.

Язык: Английский

---

Design, synthesis of 2-phenyl-1H-benzo[d]imidazole derivatives as 17β-HSD10 inhibitor for the treatment of Alzheimer's Disease

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

It has been reported that 17β-HSD10 plays a key role in Alzheimer's disease. Here, total of 44 2-phenyl-1H-benzo[d]imidazole derivatives were designed and synthesized as novel inhibitors based on rational design SAR studies. Among them, compound 33 (N-(4-(1,4,6-trimethyl-1H-benzo[d] imidazol-2-yl)phenyl)cyclohexanecarboxamide) showed high inhibitory efficacy (17β-HSD10 IC50 = 1.65 ± 0.55 μM) low toxicity (HepaRG >100 μM). The Morris water maze experiment revealed could alleviate cognitive impairment induced by scopolamine mice. This study facilitates the further development more potent for treatment

Язык: Английский

---

Targeting gut microbiota as a therapeutic approach for neurodegenerative diseases

Neuroprotection/Neuroprotection (Chichester, England. Print), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Abstract Recent evidence suggests a more important role of the gut microbiota in neurodegenerative diseases (NDDs) given its relationship through microbiota‐gut‐brain as an active communication system aiding maintaining homeostasis between brain and gut. This review focuses on how modulation can serves therapeutic strategy for NDDs, emphasizing neuroprotective effects probiotics. Probiotics are live microorganisms that confer health benefits, their interaction with gut‐microbiota influences neurogenesis, neurotransmitter regulation, neuroinflammation. advancements, including germ‐free animal models, fecal transplantation (FMT), diverse probiotic strains, have revealed underlying mechanisms linking to function. Notably, several Lactobacillus Bifidobacterium species been shown exert via upregulation neurotrophic factors such brain‐derived factor enhancing mitochondrial function reducing impacts oxidative stress. Interestingly, FMT has exhibited degree success overcoming cognitive impairment motor deficits preclinical studies clinical trials. However, further research is warranted explore potential humans. Overall, this highlights significant NDDs advocates gut‐targeted interventions innovative approaches mitigate these diseases.

Язык: Английский

---

A Novel Frontier in Gut–Brain Axis Research: The Transplantation of Fecal Microbiota in Neurodegenerative Disorders

Biomedicines, Год журнала: 2025, Номер 13(4), С. 915 - 915

Опубликована: Апрель 9, 2025

The gut–brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous (CNS) and gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s (AD), sclerosis (MS), amyotrophic lateral (ALS). In recent years, fecal transplantation (FMT) gained attention an innovative therapeutic approach, aiming to restore microbial balance while influencing neuroinflammatory review explores mechanisms by which FMT impacts axis. Key areas of focus include its ability reduce neuroinflammation, strengthen barrier integrity, regulate neurotransmitter production, reinstate diversity. Both preclinical clinical studies indicate that can alleviate motor cognitive deficits PD AD, lower markers MS, enhance respiratory neuromuscular functions ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, inconsistencies outcomes. Innovations synthetic communities, engineered probiotics, AI-driven analysis microbiome hold potential improve precision effectiveness managing conditions. Although presents considerable promise development, widespread application for diseases requires thorough validation well-designed, large-scale trials. It is essential establish standardized protocols, refine processes, deepen our understanding molecular behind efficacy.

Язык: Английский

---

The role of gut microbiota‐derived metabolites in neuroinflammation

Neuroprotection/Neuroprotection (Chichester, England. Print), Год журнала: 2025, Номер unknown

Опубликована: Март 15, 2025

Abstract Neuroinflammation, a key defense mechanism of the nervous system, is associated with changes in inflammatory markers and stimulation neuroimmune cells such as microglia astrocytes. Growing evidence indicates that gut microbiota its metabolites directly or indirectly regulate host health. According to recent studies, bacterial dysbiosis closely linked several central system disorders cause neuroinflammation, including multiple sclerosis, Alzheimer's disease, Parkinson's sepsis‐associated encephalopathy, ischemic stroke. Recent findings indicate bidirectional communication network between influences neuroinflammation cognitive function. Dysregulation this can affect generation cytotoxic metabolites, promote impair cognition. This review explores lesser‐studied microbiota‐derived involved neuroinflammation—bile acids, trimethylamine‐N‐oxide, indole derivatives—as targets for creating new treatment tools neuroinflammatory illnesses, well possible biomarkers early diagnosis prognosis.

Язык: Английский

---

Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression

Frontiers in Microbiology, Год журнала: 2025, Номер 16

Опубликована: Апрель 17, 2025

As a significant mental health disorder worldwide, the treatment of depression has long faced challenges low rate, drug side effects and high relapse rate. Recent studies have revealed that gut microbiota neuronal mitochondrial dysfunction play central roles in pathogenesis depression: influences course through multiple pathways, including immune regulation, HPA axis modulation neurotransmitter metabolism. Mitochondrial function serves as key hub mediates mood disorders mechanisms such defective energy metabolism, impaired neuroplasticity amplified neuroinflammation. Notably, bidirectional regulatory network exists between mitochondria: flora metabolite butyrate enhances biosynthesis activation AMPK–PGC1α pathway, whereas reactive oxygen species produced by mitochondria counteract composition altering intestinal epithelial microenvironment. In this study, we systematically potential pathways which improves regulating synthesis, autophagy, oxidative stress homeostasis proposed integration probiotic supplementation, dietary fiber intervention, fecal microbial transplantation to remodel flora–mitochondrial axis, provides theoretical basis for development novel antidepressant therapies targeting gut–brain interactions.

Язык: Английский

---

The Complex Relationship Between Gut Microbiota and Alzheimer’s Disease: A Systematic Review

Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102637 - 102637

Опубликована: Дек. 1, 2024

Alzheimer's disease (AD) is a progressive, degenerative disorder of the central nervous system. Despite extensive research conducted on this disorder, its precise pathogenesis remains unclear. In recent years, microbiota-gut-brain axis has attracted considerable attention within field AD. The gut microbiota communicates bidirectionally with system through gut-brain axis, and alterations in structure function can influence progression Consequently, regulating to mitigate AD emerged as novel therapeutic approach. Currently, numerous studies concentrate intrinsic relationship between paper, we summarize multifaceted role present detailed strategies targeting microbiota, including treatment Traditional Chinese Medicine (TCM), which garnered increasing years. Finally, discuss potential for modulating alleviate AD, current challenges area research, provide an outlook future directions field.

Язык: Английский

---

mGluR7: the new player protecting the central nervous system

Ageing Research Reviews, Год журнала: 2024, Номер 102, С. 102554 - 102554

Опубликована: Окт. 24, 2024

Язык: Английский

---