Advances in the study of the effects of gut microflora on microglia in Alzheimer’s disease DOI Creative Commons

Jin-Jing Wu,

Zhe Wei

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Nov. 30, 2023

Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, caused by various factors including β-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction microglia has been associated with the onset advancement different neurodevelopmental neurodegenerative disorders, such as AD. gut mammals harbors vast complex population microorganisms, commonly referred to microbiota. There's growing recognition that these microbes are intrinsically intertwined mammalian physiology. Through circulation metabolites, they establish metabolic symbiosis, enhance immune function, communication remote cells, those in brain. microbiome plays crucial part influencing development performance microglia, indicated recent preclinical studies. Dysbiosis intestinal flora leads alterations transcriptome regulate interconversion subtypes. This conversation explores research clarifies how bacteria, their byproducts, harmful elements affect activation characteristics microglia. understanding opens doors innovative microbial-based therapeutic strategies for early identification treatment goals

Language: Английский

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets DOI Creative Commons
Zdeněk Fišar

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1676 - 1676

Published: Nov. 11, 2022

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, synaptic nonsynaptic plasticity the lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury synapses neurons accumulation extracellular amyloid plaques intracellular neurofibrillary tangles are considered main morphological neuropathological features AD. Age, genetic epigenetic factors, environmental stressors, lifestyle contribute risk AD onset progression. These factors associated with structural functional changes brain, leading cognitive decline. Biomarkers reflect cause specific function, especially pathways neurotransmission, neuroinflammation, bioenergetics, apoptosis, oxidative nitrosative stress. Even initial stages, is Aβ neurotoxicity, mitochondrial dysfunction, tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that primary neurotoxicity oligomers oligomers, their mutual synergy. For development new efficient drugs, targeting elimination potentiation effects, unwanted protein interactions biomarkers (mainly dysfunction) early stage seems promising.

Language: Английский

Citations

53
Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice DOI Creative Commons
Xiaohang Qian, Wangxi Hai, Siyue Chen

et al.

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Nov. 22, 2023

Numerous studies have described the notable impact of gut microbiota on brain in Alzheimer's disease (AD) via – axis. However, molecular mechanisms underlying involvement development AD are limited. This study aimed to explore potential by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months age were used as mouse model. Cognitive function was assessed using Morris water maze test. The levels Aβ plaque neuroinflammation detected immunofluorescence PET/CT. addition, we not only 16S rRNA gene sequencing metabolomics variation characteristics serum metabolism abundance, but also combined spatial transcriptomics change identify their correlation. showed significant cognitive impairment amyloid-β deposits brain. abundance significantly changed mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, Ruminococcus increased Pseudomonas. integration untargeted that glycerophospholipid a common alteration pathway mice. Significant proliferation activation astrocyte microglia observed accompanied alterations immune pathways. Integration analysis fecal transplantation (FMT) intervention revealed association microbiota, host metabolism,

Language: Английский

Citations

37
Myricetin improves pathological changes in 3×Tg-AD mice by regulating the mitochondria-NLRP3 inflammasome-microglia channel by targeting P38 MAPK signaling pathway DOI
Pengfei Liu, Yunfeng Zhou,

Jun-Zhuo Shi

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 115, P. 154801 - 154801

Published: April 6, 2023

Language: Английский

Citations

27
Therapeutic potential of hydrogen-rich water in zebrafish model of Alzheimer’s disease: targeting oxidative stress, inflammation, and the gut-brain axis DOI Creative Commons
Jiaxuan He,

Peiye Xu,

Ting Xu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 7, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder, with amyloid-beta (Aβ) aggregation playing key role in its pathogenesis. Aβ-induced oxidative stress leads to neuronal damage, mitochondrial dysfunction, and apoptosis, making antioxidative strategies promising for AD treatment. This study investigates the effects of hydrogen-rich water (HRW) zebrafish model. Zebrafish were exposed aluminum chloride induce AD-like pathology then treated HRW using nanobubble device. Behavioral assays, ELISA, Hematoxylin-eosin (H&E) staining, reactive oxygen species (ROS) neutrophil fluorescence labeling employed assess HRW's impact. Additionally, 16S rRNA sequencing analyzed effect on gut microbiota. can significantly improve cognitive impairment depression-like behavior model, reduce Aβ deposition (p < 0.0001), regulate liver Soluble epoxide hydrolase (sEH) levels 0.05), neuroinflammation, stress. Furthermore, reduced number harmful bacteria linked by restoring balance microbiota gut. These findings suggest that has potential as therapeutic strategy targeting stress, inflammation, gut-brain axis modulation.

Language: Английский

Citations

1
Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis DOI Creative Commons
Yihang Zhao, Mengzhen Jia, Chen Ding

et al.

iMeta, Journal Year: 2025, Volume and Issue: 4(2)

Published: Feb. 21, 2025

Abstract Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via gut‐brain axis remains elusive. In a clinical trial, we observed, first time, that 4‐month TRF ameliorated impairments among Alzheimer's disease (AD) patients. Experiments 5xFAD mice corroborated gut microbiota‐dependent effect of on mitigating dysfunction, amyloid‐beta deposition, and neuroinflammation. Multi‐omics integration linked Bifidobacterium pseudolongum ( B. ) propionic acid (PA) with key genes AD pathogenesis. Oral supplementation or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood‐brain barrier penetration, while knockdown free fatty receptor 3 (FFAR3) diminished benefits. Notably, observed positive correlation between fecal improved function an cohort, further indicating enhanced production. These findings highlight microbiota‐metabolites‐brain as pivotal benefits, proposing potential therapies.

Language: Английский

Citations

1
Frequent fecal microbiota transplantation improves cognitive impairment and pathological changes in Alzheimer’s disease FAD4T mice via the microbiota-gut-brain axis DOI Creative Commons
Zhiyan Zou, Dan Lei, Yin Yuan

et al.

Heliyon, Journal Year: 2025, Volume and Issue: unknown, P. e42925 - e42925

Published: Feb. 1, 2025

Language: Английский

Citations

1
Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF‐кB pathway through microbiota‐gut‐brain axis DOI
Zhi‐Tong Zhang,

Si‐Min Deng,

Chong Chen

et al.

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(8), P. 3522 - 3542

Published: April 10, 2023

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being crucial factor in its pathogenesis. Pterostilbene well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting potential medicinal advantages for treating DCI. Therefore, this study to explore the beneficial effects of pterostilbene improving dysfunction DCI mice. A diabetic model was induced high-fat diet plus streptozotocin (40 mg·kg-1 ) consecutive 5 days. After animals were confirmed be state, they treated (20 or 60 , i.g.) 10 weeks. Pharmacological evaluation showed could ameliorate dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce accumulation β-amyloid alleviated neuroinflammation suppressing oxidative stress carbonyl astrocyte microglia activation, dopaminergic loss. Further investigations reduced level lipopolysaccharide, modulated colon brain TLR4/NF-κB signaling pathways, decreased release inflammatory factors, which turn inhibited intestinal neuroinflammation. Furthermore, also homeostasis microbiota, increase levels short-chain fatty acids their receptors, suppress loss tight junction proteins. In addition, results plasma non-targeted metabolomics revealed modulate differential metabolites metabolic pathways associated inflammation, thereby systemic Collectively, our found first time alleviate inhibiting pathway through microbiota-gut-brain axis, may one mechanisms neuroprotective effects.

Language: Английский

Citations

19
The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies DOI Creative Commons
Yu Zhan, Murad Al‐Nusaif, Cong Ding

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: April 27, 2023

Being isolated from the peripheral system by blood–brain barrier, brain has long been considered a completely impervious tissue. However, recent findings show that gut microbiome (GM) influences gastrointestinal and disorders such as Alzheimer’s disease (AD). Despite several hypotheses, neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, oxidative stress, being proposed to explain origin progression of AD, pathogenesis remains incompletely understood. Epigenetic, molecular, pathological studies suggest GM AD development have endeavored find predictive, sensitive, non-invasive, accurate biomarkers for early diagnosis monitoring progression. Given growing interest in involvement current research endeavors identify prospective both preclinical clinical diagnoses, well targeted therapy techniques. Here, we discuss most on changes microbiome-based biomarkers, diagnostic uses, approaches. Furthermore, addressed herbal components, which could provide new venue research.

Language: Английский

Citations

15
Causal association between colorectal cancer and Alzheimer’s disease: a bidirectional two-sample mendelian randomization study DOI Creative Commons

Chunsheng Yuan,

Saisai Liu,

Kezhen Yang

et al.

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 5, 2024

Background: Colorectal cancer and Alzheimer’s disease are both common life-threatening diseases in the elderly population. Some studies suggest a possible inverse relationship between colorectal disease, but real-world research is subject to many biases. We hope clarify causal two through bidirectional two-sample Mendelian randomization study. Methods: In our study, we used genetic summary data from large-scale genome-wide association investigate disease. Our primary analysis employed inverse-variance weighted method also complementary techniques, including MR-Egger, median estimator, Maximum likelihood. applied simex adjustment MR-Egger results. utilized MRlap package detect potential sample overlap its impact on bias of addition, performed several sensitivity heterogeneity analyses, ensure reliability Results: The combined effect size results indicate that may decrease incidence with an odds ratio (OR) 0.846 (95% CI: 0.762–0.929). Similar were observed using other methods such as On hand, slightly increase cancer, OR 1.014 1.001–1.027). However, one subgroup not significant, indicated introduced into Therefore, reverse validation reliable. F-statistic for all SNPs was greater than 20. Four related outcome excluded Phenoscanner website did affect overall direction these statistics further validated by MR-PRESSO, funnel plots, leave-one-out Cochran’s Q, demonstrating findings. Conclusion: According findings this there appears be These could have important implications clinical practice terms how treated. To better understand diseases, more screening needed settings.

Language: Английский

Citations

5
Antibiotic-induced gut microbe dysbiosis alters neurobehavior in mice through modulation of BDNF and gut integrity DOI
Eman H. Thabet,

Abeer E. Dief,

Shams A-F Arafa

et al.

Physiology & Behavior, Journal Year: 2024, Volume and Issue: 283, P. 114621 - 114621

Published: June 24, 2024

Language: Английский

Citations

5