Alzheimer s Research & Therapy, Journal Year: 2023, Volume and Issue: 15(1)
Published: May 31, 2023
Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but mechanisms through which bacteria influence brain are still unclear. This study tests hypothesis that GM and mediators of microbiota-gut-brain axis (MGBA) associated with amyloid cascade in sporadic AD.
Language: Английский
Nutrients, Journal Year: 2022, Volume and Issue: 14(3), P. 668 - 668
Published: Feb. 5, 2022
Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation implicated in the pathogenesis several gastrointestinal extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through increasingly defined brain axis, opening possibility for new microbiota-based therapeutic options. Although studies conducted unravel possible relationship between Alzheimer’s Disease (AD) progression, diagnostic potential approaches aiming at restoring eubiosis remain be fully addressed. In this narrative review, we briefly summarize role homeostasis health disease, present evidence AD patients. Based on these observations, then discuss how dysbiosis might exploited tool early advanced stages, examine prebiotics, probiotics, fecal transplantation, diets complementary interventions thus offering insights into diagnosis treatment devastating progressive disease.
Language: Английский
Citations
165
Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)
Published: Feb. 1, 2023
Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline cognition. There are currently few effective modifying therapies for AD, but insights into mechanisms that mediate onset and progression may lead to new, therapeutic strategies. Amyloid beta oligomers plaques, tau aggregates, neuroinflammation play critical role neurodegeneration impact clinical AD progression. The upstream modulators these pathological features have not been fully clarified, recent evidence indicates gut microbiome (GMB) an influence on therefore human patients. In this review, we summarize studies identified alterations GMB correlate with pathophysiology patients mouse models. Additionally, discuss findings manipulations models potential GMB-targeted therapeutics AD. Lastly, diet, sleep, exercise as modifiers relationship between conclude future directions recommendations further topic.
Language: Английский
Citations
154
Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)
Published: June 17, 2022
A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.
Language: Английский
Citations
126
Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 912 - 933
Published: Sept. 8, 2023
Language: Английский
Citations
105
Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)
Published: June 15, 2022
This review provides an overview of the importance microbiota in regulation gut-brain communication immune-related neurological disorders. The gastrointestinal (GI) tract hosts a diverse abundance microbiota, referred to as gut microbiota. plays role maintenance GI homeostasis and is likely have multiple effects on brain development function. bidirectional between termed microbiota-gut-brain axis. intestine appears affect human health behavior, certain animal studies demonstrated association alterations Most insights about axis come from germ-free models, which reveal neural To date, many observed impact patients with Although investigated axis, there are still limitations translating this research humans given complexities relationship brain. In review, we discuss emerging evidence how regulates function through biological networks, well possible contribution
Language: Английский
Citations
99
Circulation Research, Journal Year: 2022, Volume and Issue: 130(8), P. 1112 - 1144
Published: April 14, 2022
The microbiota-gut-brain-axis (MGBA) is a bidirectional communication network between gut microbes and their host. Many environmental host-related factors affect the microbiota. Dysbiosis defined as compositional functional alterations of microbiota that contribute to pathogenesis, progression treatment responses disease. occurs when perturbations composition function exceed ability its host restore symbiotic state. leads dysfunctional signaling MGBA, which regulates development host’s immune, metabolic, nervous systems. Dysbiosis-induced dysfunction MGBA seen with aging stroke, linked common stroke risk such obesity, diabetes, atherosclerosis. Changes in are also response may impair recovery after injury. This review will begin an overview tools used study discussion on limitations potential experimental confounders. Relevant components introduced summarized for better understanding age-related changes stroke. We then focus relationship aging, highlighting all undergo can be influenced by or even driven In final section, current clinical preclinical evidence role hypertension, frailty summarized, well populations. conclude describing microbiota-based therapies including use pre-/pro-biotics supplementations bacterial metabolites. Ongoing progress this new frontier biomedical sciences lead improved MGBA’s impact human health
Language: Английский
Citations
95
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572
Published: Sept. 12, 2022
Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target
Language: Английский
Citations
92
Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1252 - 1252
Published: Jan. 1, 2022
Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number physiological and pathological processes in human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that mediators interactions involved occurrence development many neurodegenerative diseases, including Alzheimer's disease. This review summarizes current research potential roles mechanisms AD. First, we introduce metabolic distribution, specific receptors signaling pathways body. The concentration levels AD patient/animal models then summarized. In addition, illustrate effects cognitive level, features (Aβ tau) neuroinflammation Finally, analyze translational value therapeutic targets for treatment
Language: Английский
Citations
80
Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 12(2)
Published: Feb. 1, 2023
Abstract The gut microbiota represents a diverse and dynamic population of microorganisms that can influence the health host. Increasing evidence supports role as key player in pathogenesis neurodegenerative diseases, including Alzheimer's disease (AD). Unfortunately, mechanisms behind interplay between pathogens AD are still elusive. It is known bacteria‐derived outer membrane vesicles (OMVs) act natural carriers virulence factors central players bacteria. Helicobacter pylori ( H. ) common gastric pathogen infection has been associated with an increased risk to develop AD. Here, we first shed light on OMVs derived from brain healthy conditions pathology case Our results reveal cross biological barriers, eventually reaching brain. Once brain, these taken up by astrocytes, which induce activation glial cells neuronal dysfunction, ultimately leading exacerbated amyloid‐β cognitive decline. Mechanistically, identified critical for complement component 3 (C3)‐C3a receptor (C3aR) signalling mediating interaction microglia neurons upon presence OMVs. Taken together, our study reveals detrimental effect functionality accelerates development via C3‐C3aR signalling.
Language: Английский
Citations
78
Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102690 - 102690
Published: March 27, 2023
The brain is particularly susceptible to oxidative damage which a key feature of several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's (PD) and Huntington's disease. shuttling glutathione (GSH) precursors from astrocytes neurons has been shown be instrumental for the neuroprotective activity. Here, we revealed that short chain fatty acids (SCFA), have related AD PD, could promote glutamate-glutamine shuttle potentially resist in at cellular level. Furthermore, performed nine-month-long dietary SCFA supplementations APPswe/PS1dE9 (APP/PS1) mice, showed it reshaped homeostasis microbiota alleviated cognitive impairment by reducing Aβ deposition tau hyperphosphorylation. Single-cell RNA sequencing analysis hippocampus can enhance astrocyte-neuron communication shuttle, mainly acting on astrocyte vivo. Collectively, our findings indicate long-term early aging stage regulate neuroenergetics alleviate AD, providing promising direction development new drug.
Language: Английский
Citations
69