scholarly journals The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 934
Author(s):  
Tiziana Bisogno ◽  
Anna Lauritano ◽  
Fabiana Piscitelli

Alzheimer’s disease (AD) is a neurodegenerative disease that progresses from mild cognitive impairment to severe dementia over time. The main clinical hallmarks of the disease (e.g., beta-amyloid plaques and neurofibrillary tangles) begin during preclinical AD when cognitive deficits are not yet apparent. Hence, a more profound understanding of AD pathogenesis is needed to develop new therapeutic strategies. In this context, the endocannabinoid (eCB) system and the gut microbiome are increasingly emerging as important players in maintaining the general homeostasis and the health status of the host. However, their interaction has come to light just recently with gut microbiota regulating the eCB tone at both receptor and enzyme levels in intestinal and adipose tissues. Importantly, eCB system and gut microbiome, have been suggested to play a role in AD in both animal and human studies. Therefore, the microbiome gut-brain axis and the eCB system are potential common denominators in the AD physiopathology. Hence, the aim of this review is to provide a general overview on the role of both the eCB system and the microbiome gut-brain axis in AD and to suggest possible mechanisms that underlie the potential interplay of these two systems.

2018 ◽  
Vol 15 (13) ◽  
pp. 1179-1190 ◽  
Author(s):  
Vilma M. Junges ◽  
Vera E. Closs ◽  
Guilherme M. Nogueira ◽  
Maria G.V. Gottlieb

The role of diet and gut microbiota in the pathophysiology of neurodegenerative diseases, such as Alzheimer's, has recently come under intense investigation. Studies suggest that human gut microbiota may contribute to the modulation of several neurochemical and neurometabolic pathways, through complex systems that interact and interconnect with the central nervous system. The brain and intestine form a bidirectional communication axis, or vice versa, they form an axis through bi-directional communication between endocrine and complex immune systems, involving neurotransmitters and hormones. Above all, studies suggest that dysbiotic and poorly diversified microbiota may interfere with the synthesis and secretion of neurotrophic factors, such as brain-derived neurotrophic factor, gammaaminobutyric acid and N-methyl D-Aspartate receptors, widely associated with cognitive decline and dementia. In this context, the present article provides a review of the literature on the role of the gutbrain axis in Alzheimer's disease.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.


2022 ◽  
pp. 354-376
Author(s):  
Sourav Samanta ◽  
Madhu Ramesh ◽  
Ashish Kumar ◽  
Thimmaiah Govindaraju

2021 ◽  
Author(s):  
Júlia Maia Seixas ◽  
Hygor Kleber Cabral Silva ◽  
Maria Alice Rocha Lopes ◽  
Kamila Castro Oliveira Camargos ◽  
Lara Silveira Marques ◽  
...  

Background: Alzheimer’s disease (AD) is the most common cause of dementia among older adults impacting quality of life. Nowadays, four drugs are indicated to manage AD symptoms, however, none of them have shown effectiveness to prevent the disease’s progress, and they are associated with adverse effects. In this scenario, the endocannabinoid system has the attention of researchers and physicians, because of its relation with processes involved in the AD physiopathology. Therefore, in the last decade, studies that evaluate the use of Cannabidiol (CBD) and other phytocannabinoids, like tetrahydrocannabinol (THC) and cannabinol (CBN), as an alternative treatment to this illness, have multiplied. Objectives: To bring updated information about this new and promising therapeutic. Methods: A bibliographic research in PubMed with the terms “Cannabidiol and Alzheimer” was made, with the filters “Free full text” and “Publication Date 5 years”. The research obtained 31 results, from which were chosen 10. Results: In vivo studies with CBD, THC and CBN have shown their properties: anti-inflammatory, antioxidant, attenuation of toxic accumulation of β-amyloid protein and to reverse cognitive deficits, all AD physiopathological processes. It was also demonstrated that the combination between THC and CBD shows better efficiency and fewer adverse effects than CBD isolated use. Conclusions: Despite needing deeper and stronger studies with better conducted clinical trials, the researches about phytocannabinoids use in AD seem promising, and they might become the biggest ally in the treatment of this and other neurodegenerative conditions.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Luca ◽  
Maurizio Di Mauro ◽  
Marco Di Mauro ◽  
Antonina Luca

Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer’s disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer’s disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.


Gut ◽  
2022 ◽  
pp. gutjnl-2021-326269
Author(s):  
Chun Chen ◽  
Jianming Liao ◽  
Yiyuan Xia ◽  
Xia Liu ◽  
Rheinallt Jones ◽  
...  

ObjectiveThis study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer’s disease (AD) pathogenesis.DesignWe analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors.ResultsMicrobial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology in germ-free 3×Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3×Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients’ gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors’ microbiota transplants.ConclusionsThese findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.


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