The gut microbiome in neurological disorders

Cryan, John F.; O’Riordan, Kenneth J.; Sandhu, Kawaljit Singh; Peterson, Veronica L.; Dinan, Timothy G.

doi:10.1016/s1474-4422(19)30356-4

Cited by 864 publications

(626 citation statements)

References 119 publications

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“…ENS is a network of neurons structured in the submucosal and myenteric plexus and is largely responsible for the coordination of gut motility [159]. ENS and CNS share structure and neurochemistry.…”

Section: Enteric Nervous Systemmentioning

confidence: 99%

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Forte

Fernández-Rilo

Palomba

et al. 2020

IJMS

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The hypothalamus regulates energy homeostasis by integrating environmental and internal signals to produce behavioral responses to start or stop eating. Many satiation signals are mediated by microbiota-derived metabolites coming from the gastrointestinal tract and acting also in the brain through a complex bidirectional communication system, the microbiota–gut–brain axis. In recent years, the intestinal microbiota has emerged as a critical regulator of hypothalamic appetite-related neuronal networks. Obesogenic high-fat diets (HFDs) enhance endocannabinoid levels, both in the brain and peripheral tissues. HFDs change the gut microbiota composition by altering the Firmicutes:Bacteroidetes ratio and causing endotoxemia mainly by rising the levels of lipopolysaccharide (LPS), the most potent immunogenic component of Gram-negative bacteria. Endotoxemia induces the collapse of the gut and brain barriers, interleukin 1β (IL1β)- and tumor necrosis factor α (TNFα)-mediated neuroinflammatory responses and gliosis, which alter the appetite-regulatory circuits of the brain mediobasal hypothalamic area delimited by the median eminence. This review summarizes the emerging state-of-the-art evidence on the function of the “expanded endocannabinoid (eCB) system” or endocannabinoidome at the crossroads between intestinal microbiota, gut-brain communication and host metabolism; and highlights the critical role of this intersection in the onset of obesity.

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Section: Enteric Nervous Systemmentioning

confidence: 99%

Obesity Affects the Microbiota–Gut–Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators

Forte

Fernández-Rilo

Palomba

et al. 2020

IJMS

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“…They contained abnormal numbers of several immune cell types and altered cytokines, as well as deficits in local and systematic lymphoid structure. GF animals showed significant differences in a variety of ENS/CNS diseases, such as neurodegenerative disorders, anxiety, depression, reduction of brain-derived neurotrophic factor (BDNF) gene expression in the amygdala and hippocampus, increased permeability of the blood-brain barrier (BBB), hypothalamic-pituitary-adrenal axis (HPA) hyperactivation, and dysfunction of the microglia [48,49].…”

Section: Gut Microbiota and Immune Protectionmentioning

confidence: 99%

“…Firstly, they are able to produce and secrete bacterio-toxins, such as bacteriocins, which can block pathogen adhesion to epithelial cells and inhibit bacterial invasion. Members of the Lactobacillus genus produce lactic acid, which, in addition to creating an inhibitory environment for the growth of many bacteria, potentiate the antimicrobial activity of the host lysozyme by disrupting the bacterial outer membrane [49]. Secondly, probiotics compete with potential pathogenic bacteria for binding sites and for nutrients [35].…”

Section: Probiotics As New Therapymentioning

confidence: 99%

Gut–Brain Axis: Focus on Neurodegeneration and Mast Cells

2020

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Many studies highlighted that a bidirectional communication between the gut and the central nervous system (CNS) exists. A vigorous immune response to antigens must be avoided, and pathogenic organisms crossing the gut barrier must be detected and killed. For this reason, the immune system developed fine mechanisms able to maintain this delicate balance. The microbiota is beneficial to its host, providing protection against pathogenic bacteria. It is intimately involved in numerous aspects of host physiology, from nutritional status to behavior and stress response. In the last few years, the implication of the gut microbiota and its bioactive microbiota-derived molecules in the progression of multiple diseases, as well as in the development of neurodegenerative disorders, gained increasing attention. The purpose of this review is to provide an overview of the gut microbiota with particular attention toward neurological disorders and mast cells. Relevant roles are played by the mast cells in neuroimmune communication, such as sensors and effectors of cytokines and neurotransmitters. In this context, the intake of beneficial bacterial strains as probiotics could represent a valuable therapeutic approach to adopt in combination with classical therapies. Further studies need to be performed to understand if the gut bacteria are responsible for neurological disorders or if neurological disorders influence the bacterial profile.

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“…Since then, growing evidence confirms that the gut microbiome can be considered the "microbial organ" of the body (O'Hara and Shanahan, 2006;Byndloss and Bäumler, 2018), acting through multiple mechanisms (e.g., microbiotaderived metabolites (Schroeder and Bäckhed, 2016;Dalile et al, 2019) and microbial translocation (Manfredo Vieira et al, 2018;Meisel et al, 2018)) to communicate with the host and regulate host physiology at both local and systemic levels. It is believed that the gut microbiome can affect host metabolism (Tilg et al, 2020), immunity (Belkaid and Harrison, 2017), endocrine (Rooks and Garrett, 2016;Rastelli et al, 2019), and neural function (Sharon et al, 2016) and thus contribute to host susceptibility to a series of diseases (Sekirov et al, 2010;Clemente et al, 2012;Nicholson et al, 2012;Lynch and Pedersen 2016), such as obesity (Le Chatelier et al, 2013;Ridaura et al, 2013), diabetes (Qin et al, 2012), fatty liver diseases (Canfora et al, 2019), cardiovascular diseases (Schiattarella et al, 2017), autoimmune and inflammatory diseases (Clemente et al, 2018), psychological and neurological disorders (Cryan et al, 2020), and cancer (Garrett, 2015;Yu and Schwabe, 2017;Vitiello et al, 2019). Seven facts and five initiatives for gut microbiome research…”

Section: Fact 3 the Gut Microbiome Contributes To Health And Diseasesmentioning

confidence: 99%