Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome

Opeyemi, Oluwasinmisola; Rogers, Matthew B.; Firek, Brian; Janesko‐Feldman, Keri; Vagni, Vincent; Mullett, Steven J.; Wendell, Stacy G.; Nelson, Brittany P.; New, Lee Ann; Mariño, Eliana; Kochanek, Patrick M.; Bayır, Hülya; Clark, Robert S. B.; Morowitz, Michael J.; Simon, Dennis

doi:10.1089/neu.2020.7506

Cited by 31 publications

(28 citation statements)

References 52 publications

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“…Acute brain injury, such as IPH induces gut microbiota transformation from the up taxonomic levels and forms a new bacterial interaction network to compensate the bacterial alpha diversity at the low taxonomic levels in the gut. Phylum Verrucomicrobiota enrichment can specifically distinguish IPH patients from healthy people, similar to the finding that family Verrucomicrobiaceae is enriched in the gut of mice suffering traumatic brain injury ( Opeyemi et al., 2021 ). This phylum, Akkermansia muciniphila , a next-generation probiotic ( O'Toole et al., 2017 ), is the main differential species ( Table S3 ).…”

Section: Discussionsupporting

confidence: 72%

“…Furthermore, the neuroactive compounds were diversified in the patients’ specific-group species. In addition to the common compounds synthesized by each species, such as glutamate and quinolinic acid, the patient’s group-specific species produce additional beneficial molecules, such as butyrate and propionate, which alleviate deteriorate factors, like inflammation state and metabolic disorders, thereby improving the functional outcomes ( Vipperla and O'Keefe, 2012 ; Opeyemi et al., 2021 ). Therefore, we hypothesized that the altered gut bacterial composition and function is another mechanism after suffering IPH through which the gut microbiota transformation might alleviate the adverse effects and promote neural recovery, thereby improving the outcomes in patients.…”

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: Discussionsupporting

confidence: 72%

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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“…TBI mice treated by Clostridium butyricum also improved neurological deficits, attenuates brain edema, ameliorated neurodegeneration, and alleviated BBB impairment via elevating intestinal Glucagonlike peptide 1(GLP-1) secretion (93). SCFAs supplementation also improved spatial learning following CCI-induced TBI, mediated by activating the neurotrophic tyrosine kinase receptor type 1 (TrkA) pathway (95,102). Probiotic supplementation also significantly remedied the gut microbiota dysbiosis and decreased the intestinal permeability following experimental TBI by reducing the intestinal mucosa damage, alleviating brain injury (103).…”

Section: Wdi Micementioning

confidence: 99%

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

Yuan

2021

Front. Immunol.

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Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.

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“…Consistent with the general model of the gut–brain axis, SCFA metabolism seems to be a critical element of TBI-induced gut dysbiosis. The abundance of SCFA-producing bacteria is diminished after TBI, and SCFA supplementation is sufficient to improve neurological function [ 77 ].…”

Section: Mechanisms Of Microbiome Disruption In Neurologic Diseasementioning

confidence: 99%

“…Further, they found a higher level of activation of circulating lymphocytes and a subsequent greater degree of microglial activation in SCFA-treated mice, suggesting a potential regenerative effect on neural plasticity as the mechanism by which SCFAs may benefit poststroke recovery. Furthermore, in 2021, Opeyemi et al [ 77 ] randomized 20 experimentally induced TBI mice into a control group, receiving standard drinking water for 2 weeks before TBI, and an intervention group, receiving SCFA supplementation. The SCFA-supplemented group showed greater capacity for spatial learning measured 2 weeks post-TBI using the Morris water maze.…”

Section: Interventionsmentioning

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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Sustained Dysbiosis and Decreased Fecal Short-Chain Fatty Acids after Traumatic Brain Injury and Impact on Neurologic Outcome

Cited by 31 publications

References 52 publications

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

Gastrointestinal Microbiome and Neurologic Injury

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