Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury

Hanscom, Marie; Loane, David J.; Shea‐Donohue, Terez

doi:10.1172/jci143777

Cited by 106 publications

(96 citation statements)

References 190 publications

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“…The gut-brain axis enables the communication between the central nervous system (CNS) and enteric nervous system (ENS) sponsored by gut bacteria change ( Hanscom et al., 2021 ). The gastrointestinal dysfunction occurs in patients after cerebrovascular accidents ( Iftikhar et al., 2020 ), which might be partially caused by gut microbiota imbalance.…”

Section: Discussionmentioning

confidence: 99%

“…The neural signal-mediated gut activity, together with the activated immune system and endocrine change after IPH, could be the potential mechanism of IPH patients’ gut bacteria alteration. ( Kashyap et al., 2013 ; Gensollen et al., 2016 ; Zhu et al., 2018 ; Hanscom et al., 2021 ). Previous studies have proved that acute brain injury induces specific changes in the mice gut microbiota that affects the outcome in mice ( Benakis et al., 2016 ; Houlden et al., 2016 ; Mazarati et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Xiong

Peng

Song

et al. 2022

Front. Cell. Infect. Microbiol.

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Gut bacteria consists of 150 times more genes than humans that are vital for health. Several studies revealed that gut bacteria are associated with disease status and influence human behavior and mentality. Whether human brain injury alters the gut bacteria is yet unclear, we tested 20 fecal samples from patients with cerebral intraparenchymal hemorrhage and corresponding healthy controls through metagenomic shotgun sequencing. The composition of patients’ gut bacteria changed significantly at the phylum level; Verrucomicrobiota was the specific phylum colonized in the patients’ gut. The functional alteration was observed in the patients’ gut bacteria, including high metabolic activity for nutrients or neuroactive compounds, strong antibiotic resistance, and less virulence factor diversity. The changes in the transcription and metabolism of differential species were more evident than those of the non-differential species between groups, which is the primary factor contributing to the functional alteration of patients with cerebral intraparenchymal hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Xiong

Peng

Song

et al. 2022

Front. Cell. Infect. Microbiol.

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“…As in ischemic stroke, the brain–gut axis is functionally bidirectional after traumatic brain injury (TBI); in recent mouse studies, neurological injury appears to induce gut dysbiosis which in turn aggravates neuroinflammation and worsens outcome [ 54 , 75 ]. Gut-dysbiosis-induced neuroinflammation seems to be at least partially mediated by microglia and astrocytes, which have also been shown to be regulated by enteric metabolites [ 54 , 61 , 64 ].…”

Section: Mechanisms Of Microbiome Disruption In Neurologic Diseasementioning

confidence: 99%

Gastrointestinal Microbiome and Neurologic Injury

et al. 2022

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Communication between the enteric nervous system (ENS) of the gastrointestinal (GI) tract and the central nervous system (CNS) is vital for maintaining systemic homeostasis. Intrinsic and extrinsic neurological inputs of the gut regulate blood flow, peristalsis, hormone release, and immunological function. The health of the gut microbiome plays a vital role in regulating the overall function and well-being of the individual. Microbes release short-chain fatty acids (SCFAs) that regulate G-protein-coupled receptors to mediate hormone release, neurotransmitter release (i.e., serotonin, dopamine, noradrenaline, γ-aminobutyric acid (GABA), acetylcholine, and histamine), and regulate inflammation and mood. Further gaseous factors (i.e., nitric oxide) are important in regulating inflammation and have a response in injury. Neurologic injuries such as ischemic stroke, spinal cord injury, traumatic brain injury, and hemorrhagic cerebrovascular lesions can all lead to gut dysbiosis. Additionally, unfavorable alterations in the composition of the microbiota may be associated with increased risk for these neurologic injuries due to increased proinflammatory molecules and clotting factors. Interventions such as probiotics, fecal microbiota transplantation, and oral SCFAs have been shown to stabilize and improve the composition of the microbiome. However, the effect this has on neurologic injury prevention and recovery has not been studied extensively. The purpose of this review is to elaborate on the complex relationship between the nervous system and the microbiome and to report how neurologic injury modulates the status of the microbiome. Finally, we will propose various interventions that may be beneficial in the recovery from neurologic injury.

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“…Traumatic injury to the brain has acute, large-scale systemic consequences (1) that affect almost all organs and may lead to a compromised function of the heart, lung, gastrointestinal tract, liver, kidney, bones, lymphoid organs, and others, without direct systemic injury or infection (2,3). The systemic response to TBI is characterized by inflammation and, at the same time, a net systemic immunosuppression (4)(5)(6). Although brain injury results in a systemic increase of inflammatory mediators and cytokines in both patients (7)(8)(9) and rodent models of TBI (10)(11)(12), there remains ample evidence pointing toward systemic immunosuppression post-TBI, with a decrease in immune cells in the periphery (13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Fast Maturation of Splenic Dendritic Cells Upon TBI Is Associated With FLT3/FLT3L Signaling

Zhang

Chandrasekar

et al. 2022

Front. Immunol.

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The consequences of systemic inflammation are a significant burden after traumatic brain injury (TBI), with almost all organs affected. This response consists of inflammation and concurrent immunosuppression after injury. One of the main immune regulatory organs, the spleen, is highly interactive with the brain. Along this brain–spleen axis, both nerve fibers as well as brain-derived circulating mediators have been shown to interact directly with splenic immune cells. One of the most significant comorbidities in TBI is acute ethanol intoxication (EI), with almost 40% of patients showing a positive blood alcohol level (BAL) upon injury. EI by itself has been shown to reduce proinflammatory mediators dose-dependently and enhance anti-inflammatory mediators in the spleen. However, how the splenic immune modulatory effect reacts to EI in TBI remains unclear. Therefore, we investigated early splenic immune responses after TBI with and without EI, using gene expression screening of cytokines and chemokines and fluorescence staining of thin spleen sections to investigate cellular mechanisms in immune cells. We found a strong FLT3/FLT3L induction 3 h after TBI, which was enhanced by EI. The FLT3L induction resulted in phosphorylation of FLT3 in CD11c+ dendritic cells, which enhanced protein synthesis, maturation process, and the immunity of dendritic cells, shown by pS6, peIF2A, MHC-II, LAMP1, and CD68 by immunostaining and TNF-α expression by in-situ hybridization. In conclusion, these data indicate that TBI induces a fast maturation and immunity of dendritic cells which is associated with FLT3/FLT3L signaling and which is enhanced by EI prior to TBI.

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Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury

Cited by 106 publications

References 190 publications

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Gastrointestinal Microbiome and Neurologic Injury

Fast Maturation of Splenic Dendritic Cells Upon TBI Is Associated With FLT3/FLT3L Signaling

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