The Gut–CNS Axis in Multiple Sclerosis

Kadowaki, Atsushi; Quintana, Francisco J.

doi:10.1016/j.tins.2020.06.002

Cited by 74 publications

(44 citation statements)

References 139 publications

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“…Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that affects more than 2.2 million people worldwide (1). As with many autoimmune diseases, the etiology of MS is largely unknown, although a combination of genetic elements (2)(3)(4)(5) and environmental factors, including vitamin D deficiency, early-life obesity, gut dysbiosis, smoking, and infections have been associated with MS development (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

2020

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Multiple sclerosis (MS) is caused by a combination of genetic and environmental factors. It is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Previously, we developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), a murine homolog to EBV, enhanced the symptoms of experimental autoimmune encephalomyelitis (EAE), resulting in disease that more closely resembles MS in humans. Here, we explored the conditions that were necessary for EAE enhancement. We showed that latently infected CD19+IgD− B cells were capable of enhancing EAE symptoms when transferred from mice previously infected with γHV-68 into uninfected mice. We also observed a prevention of enhancement when B cells were depleted before infection. However, depletion after the establishment of latency only partially reduced EAE. This indicated the existence of a mechanism where B cells play an important role as antigen presenting cells (APCs) prior to EAE induction for the priming of Th1 cells. It is possible that these signals persist even after B cell depletion, strongly suggesting a paracrine signaling modulation of non-B cell APCs. These results strongly support the concept that EBV contributes to the development of autoimmunity and highlights the need for a vaccine against EBV that could limit or prevent multiple sclerosis development.

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Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

2020

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“…The gut and brain axis is now recognized as a key factor in the pathology of multiple neurological disorders, including MS and its experimental model EAE. 25 In EAE and MS, CD4 + effector T cells primed in the periphery migrate to the CNS, where they are reactivated by cDCs and other cells to cause myelin destruction. 98,99 In addition, recruited T cells secrete cytokines that modulate the activity of CNS-resident immune cells, such as microglia and astrocytes.…”

Section: Modulation Of Inflammation In the Central Nervous System (Cns)mentioning

confidence: 99%

“…In this review, we discuss the role of AHR in the immune response, with a focus on the gut-brain axis. 25…”

Section: Introductionmentioning

confidence: 99%

The aryl hydrocarbon receptor and the gut–brain axis

et al. 2021

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

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“…In addition, several bottom-to-top directional pathways, activated by microbiota products, are necessary for the correct development and physiological functioning of the brain [ 5 ]. Changes in the microbiota composition, the dysbiosis, contribute to several neurodegenerative disorders such as Alzheimer disease (AD) [ 2 , 5 , 6 , 7 , 8 ], Parkinson’s disease (PD) [ 9 ], multiple sclerosis (MS) [ 10 ], and amyotrophic lateral sclerosis [ 11 ].…”

Section: The Microbiota–gut–brain Axismentioning

confidence: 99%

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Giovannini

Lana

Traini

et al. 2021

JCM

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The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

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The Gut–CNS Axis in Multiple Sclerosis

Cited by 74 publications

References 139 publications

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells

The aryl hydrocarbon receptor and the gut–brain axis

The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

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