Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke

Singh, Vikramjeet; Roth, Stefan; Llovera, Gemma; Sadler, Rebecca; Garzetti, Debora; Stecher, Bärbel; Dichgans, Martin; Liesz, Arthur

doi:10.1523/jneurosci.1114-16.2016

Cited by 589 publications

(716 citation statements)

References 60 publications

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“…Very few of them have been performed in the context of vascular dementia, and none on other types of dementia, despite the clinical and physiopathologic relevance of this classification. However, the gut–brain axis also mediates the neuroinflammatory response after a vascular injury, such as ischemic stroke 124. Additionally, diabetes mellitus and obesity, which are among the main conditions predisposing to vascular dementia, are both associated with gut microbiota alterations and/or dysbiosis 125,126.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

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Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

View full text Add to dashboard Cite

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“…Acute and chronic changes in the gut microbiome following CNS injuries such as spinal cord injury and ischemic brain injury are associated with intestinal barrier dysfunction, immune dysregulation, and functional neurologic deficits 70,71 . Moreover, induction of gut dysbiosis has been demonstrated to have deleterious effects on the outcome of acute ischemic brain injury, including increased lesion volume and neuroinflammation 72–74 . Remarkably, these gut-to-brain effects are paralleled in our study which show that gut dysbiosis induced by Cr infection during chronic TBI exacerbated injury outcomes in the brain.…”

Section: Discussionmentioning

confidence: 99%

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice

Elise

Smith

Desai

et al. 2017

Brain, Behavior, and Immunity

128

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Objectives Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Methods Moderate-level TBI was induced in C57BL/6 mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Results Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28 days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. Conclusion These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury.

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“…Indeed, the microbial compositions of the gut significantly influenced outcome following stroke. This data suggests that the gut microflora is mechanistically involved in mediating the immune response to experimental brain injury, specifically through regulation of intestinal T cells 135 136 . Notably, the researchers suggest that the gut microbiota exert influence through modulating the neuroinflammatory response.…”

Section: Closing the Loop: Insights From Acute Cerebral Ischemic Eventsmentioning

confidence: 97%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

155

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke

Cited by 589 publications

References 60 publications

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

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