The association of traumatic brain injury, gut microbiota and the corresponding metabolites in mice

Wang, Shenhao; Zhu, Kaixin; Hou, Xi; Hou, Lingling

doi:10.1016/j.brainres.2021.147450

Cited by 16 publications

(13 citation statements)

References 39 publications

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“…Gut microbiota imbalance often occurs after major surgery or intestinal surgery and in critically ill patients (Earley et al, 2015;Mondot et al, 2015;Hamilton et al, 2020;Wang et al, 2020Wang et al, , 2021. Brain injury alters the composition of the intestinal microbiota, decreasing the intestinal microbial diversity (Wang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer’s Disease Model With Bilateral Intraventricular Injection of Aβ (1-42)

Wen

Wei

et al. 2022

Front. Microbiol.

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Alzheimer’s disease (AD) is a common neurodegenerative disease. More evidence has shown that gut microbiota is closely associated with AD. Also, studies have shown that the distribution of gut microbiota vary in different sections of the intestine. In this study, a rat model of AD was established using a bilateral intraventricular injection of β-amyloid (1-42) [Aβ (1-42)], and the behavior of rats, hippocampal Aβ (1-42) deposition, and the ileal and colonic microbiota in each group were analyzed. We observed that the model rats had obvious memory and cognitive impairment, increased Aβ (1-42) deposition, indicating that the AD model was successfully established. Through 16S rRNA-sequencing analysis, we found that α diversity, β diversity, and dominant microbiota in the ileum and colon of normal rats were significantly different, showing spatial heterogeneity. Additionally, the surgery and injection of Aβ (1-42) caused various degrees of disturbances in the ileal and colonic microbiota of rats. These findings provide new insights for the study of the gut microbiota of AD rats and help advance the development of therapeutic strategies for intervening AD through the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer’s Disease Model With Bilateral Intraventricular Injection of Aβ (1-42)

Wen

Wei

et al. 2022

Front. Microbiol.

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“…This results in reduced levels of putatively beneficial bacteria which in turn leads to the reduction of short-chain fatty acids (SCFAs), bacterial metabolites that play a key role in modulating metabolism, vascular response, and inflammation system-wide [ 11 , 12 ]. Dysbiosis has been shown to occur in the acute phase as early as one day post injury in rodent models [ 9 ] and humans [ 10 ]. Elucidating that TBI induces dysbiosis pinpoints the gut microbiome as a potential target to protect against the secondary injury cascade known to follow TBI [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase

Yanckello

Fanelli

McCulloch

et al. 2022

Journal of Cellular Immunology

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Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.

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“…Gene expression for tight junction protein-1 (TJP1) and occluding were analyzed according to previous real-time PCR work. 11,12 The primers were designed using Beacon Designer 3 software.…”

Section: Plos Onementioning

confidence: 99%

“…Under steady-state conditions, gut bacteria are important in the maintenance of intestinal homeostasis and immune system functioning, via the regulation of inflammatory pathways [ 11 ]. However, studies have shown that mTBI-induced dysbiosis may exacerbate deficits in gut microbiome functionality by modulating the intermediary mediators of the brain and gut; known as metabolites [ 12 ]. Rodent studies investigating the impact of RmTBI on the gut microbiome have also identified alterations to vagal nerve function [ 13 ], HPA axis [ 14 ], short chain fatty acid (SCFA) production, microglia activation [ 15 ], and intestinal and blood brain barrier (BBB) permeability [ 16 ], post injury.…”

Section: Introductionmentioning

confidence: 99%

Age matters: Microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats

et al. 2022

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Dysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)-induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in ‘beneficial bacteria’ (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.

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The association of traumatic brain injury, gut microbiota and the corresponding metabolites in mice

Cited by 16 publications

References 39 publications

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer’s Disease Model With Bilateral Intraventricular Injection of Aβ (1-42)

Marked Response of Rat Ileal and Colonic Microbiota After the Establishment of Alzheimer’s Disease Model With Bilateral Intraventricular Injection of Aβ (1-42)

Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase

Age matters: Microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats

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