The gut microbiome, endocannabinoids and metabolic disorders

Iannotti, Fabio Arturo; Marzo, Vincenzo Di

doi:10.1530/joe-20-0444

Cited by 55 publications

(65 citation statements)

References 113 publications

(119 reference statements)

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“…Studies most in the context of metabolic dysfunctions, already reviewed elsewhere [ 19 , 169 ], suggest cross-talk between the gut microbiome and the eCBome. However, the connection of the gut-brain axis and the eCBome in neurodegenerative diseases has never been deeply investigated but, considering the important role of these two systems in the physiopathology of the CNS, it is worth doing it.…”

Section: The Ecbome As the “Hidden” Player Between The Gut And The Brain In Admentioning

confidence: 99%

“…Studies performed in both AD-like animal models and patients suggested that eCB system alterations are associated with AD pathophysiology, and that its pharmacological modulation may have disease-modifying effects [ 17 , 18 ]. In the last few years, the interconnection of the eCB system and the gut microbiota has been addressed and different aspects of regulation and dysregulation of the gut microbiome and eCB system mainly in obesity and metabolic disorders excellently reviewed [ 19 , 20 ]. Recently, the eCB system and the gut microbiota dysfunctions were also reported in neuropsychiatric disorders [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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

Bisogno

Lauritano

Piscitelli

2021

Life

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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.

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Section: The Ecbome As the “Hidden” Player Between The Gut And The Brain In Admentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bisogno

Lauritano

Piscitelli

2021

Life

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“…A cannabinoid hypertonus would therefore lead to an impairment of gut permeability with an increased circulation of bacterial endotoxins, and a consequent stimulus in the synthesis and release of pro-inflammatory cytokines. A further consequence may consist in the increased transfer of these cytokines to the brain, by an increase in BBB permeability or even by transport through the afferent fibers of the vagus nerve (gut–brain axis) [ 302 , 303 ]. In fact, rimonabant, which antagonizes CB1R, reduces LPS levels and inflammation [ 304 ].…”

Section: Ecs and Gut Microbiomementioning

confidence: 99%

Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System

et al. 2021

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Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress and neuronal depletion. The broad-spectrum neuroprotective activity of the Mediterranean diet is widely documented, but it is not yet known whether its nutritional and caloric balance can induce a modulation of the endocannabinoid system. In recent decades, many studies have shown how endocannabinoid tone enhancement may be a promising new therapeutic strategy to counteract the main hallmarks of neurodegeneration. From a phylogenetic point of view, the human co-evolution between the endocannabinoid system and dietary habits could play a key role in the pro-homeostatic activity of the Mediterranean lifestyle: this adaptive balance among our ancestors has been compromised by the modern Western diet, resulting in a “clinical endocannabinoid deficiency syndrome”. This review aims to evaluate the evidence accumulated in the literature on the neuroprotective, immunomodulatory and antioxidant properties of the Mediterranean diet related to the modulation of the endocannabinoid system, suggesting new prospects for research and clinical interventions against neurodegenerative diseases in light of a nutraceutical paradigm.

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“…ECs have been found to be produced in adipose tissue, muscle (33,34), and kidneys (35), all of which are involved in the control of energy metabolism. Moreover, ECs are also produced in gut, and they in turn at a minimum influence hepatic function and signaling through the vagal afferents (25,(36)(37)(38)(39). Additionally, ECs are produced in stellate cells of liver (40) and islets of Langerhans: this review focuses on islets of Langerhans.…”

Section: General Background Of Ecs and Cbrsmentioning

confidence: 99%

An Autonomous Cannabinoid System in Islets of Langerhans

Aseer

Egan

2021

Front. Endocrinol.

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While endocannabinoids (ECs) and cannabis were primarily studied for their nervous system effects, it is now clear that ECs are also produced in the periphery where they regulate several physiological processes, including energy storage, glucose and lipid metabolism, insulin secretion and synthesis, and hepatocyte function. Within islet of Langerhans there is an autonomous EC system (ECS). Beta (β)-cells contain all the enzymes necessary for EC synthesis and degradation; ECs are generated in response to cellular depolarization; their paracrine influence on β-cells is mostly through the cannabinoid 1 receptor (CB1R) that is present on all β-cells; they modulate basal and glucose- and incretin-induced insulin secretion, and β-cell responses to various stressors. Furthermore, there is now accumulating evidence from preclinical studies that the autonomous islet ECS is a key player in obesity-induced inflammation in islets, and β-cell damage and apoptosis from many causes can be mitigated by CB1R blockers. We will thoroughly review the literature relevant to the effects of ECs and their receptors on β-cells and the other cell types within islets. Therapeutic potential of agents targeting EC/CB1R and CB2R is highly relevant because the receptors belong to the druggable G protein-coupled receptor superfamily. Present research in the ECS must be considered preliminary, especially with regards to human islet physiology, and further research is needed in order to translate basic cellular findings into clinical practice and the use of safe, clinically approved CBR modulators with and without glucose lowering combinations presently in therapeutic use for diabetes and obesity needs to be studied.

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The gut microbiome, endocannabinoids and metabolic disorders

Cited by 55 publications

References 113 publications

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

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

Mediterranean Diet and Neurodegenerative Diseases: The Neglected Role of Nutrition in the Modulation of the Endocannabinoid System

An Autonomous Cannabinoid System in Islets of Langerhans

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