Effects of Traumatic Brain Injury on the Gut Microbiota Composition and Serum Amino Acid Profile in Rats

Abstract

Traumatic brain injury (TBI) heavily impacts the body: it damages the brain tissue and the peripheral nervous system and shifts homeostasis in many types of tissue. An acute brain injury compromises the “brain–gut-microbiome axis”, a well-balanced network formed by the brain, gastrointestinal tract, and gut microbiome, which has a complex effect: damage to the brain alters the composition of the microbiome; the altered microbiome affects TBI severity, neuroplasticity, and metabolic pathways through various bacterial metabolites. We modeled TBI in rats. Using a bioinformatics approach, we sought to identify correlations between the gut microbiome composition, TBI severity, the rate of neurological function recovery, and blood metabolome. We found that the TBI caused changes in the abundance of 26 bacterial genera. The most dramatic change was observed in the abundance of Agathobacter species. The TBI also altered concentrations of several metabolites, specifically citrulline and tryptophan. We found no significant correlations between TBI severity and the pre-existing gut microbiota composition or blood metabolites. However, we discovered some differences between the two groups of subjects that showed high and low rates of neurological function recovery, respectively. The present study highlights the role of the brain–gut-microbiome axis in TBI.

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

“…Increases in bacteria belonging to the Erysipelotrichaceae family such as Faecalibaculum , as well as increases in Lachnospiraceae , both of which are considered ‘beneficial butyrate producers’ have been shown to be increased following mTBI in rodents [ 40 ] as seen in the present study. Conversely, it is commonly reported that following severe TBI there is a reduction in these ‘beneficial’ bacteria, up to 30 days following injury [ 18 , 81 ]. The exact mechanisms driving this increase in beneficial butyrate producing bacteria after injury is unknown, however, it may be a protective response to compensate for the secondary injury cascade that follows mTBI [ 82 , 83 ].…”

The role of the microbiota–gut–brain axis in long‐term neurodegenerative processes following traumatic brain injury

“…Furthermore, Peptococcaceae and Eubacterium genera of the Firmicutes phylum were also increased; however, their roles in determining TBI outcome were unclear (Houlden et al, 2016;Treangen et al, 2018). Interestingly, a clinical study in NCAA Football players with found a similar pattern of change in Lachnospiraceae bacterium A2 and Lactobacillus johnsonii after concussion (Soriano et al, 2022) as the preclinical study from Yanckello et al (2022) severe TBI animal models (Frankot et al, 2022;Treangen et al, 2018) except for the Prevotellaceae family (Taraskina et al, 2022).…”

“…Interestingly, a clinical study in NCAA Football players with found a similar pattern of change in Lachnospiraceae bacterium A2 and Lactobacillus johnsonii after concussion (Soriano et al, 2022) as the pre‐clinical study from Yanckello et al (2022) modelling a milder injury. Conversely, a clinical study in patients with chronic moderate–severe TBI did not find similar microbiota changes (Urban et al, 2020) to those in more severe TBI animal models (Frankot et al, 2022; Treangen et al, 2018) except for the Prevotellaceae family (Taraskina et al, 2022).…”

Association of sub-acute changes in plasma amino acid levels with long-term brain pathologies in a rat model of moderate-severe traumatic brain injury

“…We therefore supposed that blood concentrations of amino acids might bear some relation to the progression of TBI, thus presenting a potential diagnostic or prognostic tool. Indeed, several prior studies have examined changes in plasma or serum amino acid levels after TBI in humans (Deutschman, 1987;Flakoll et al, 1995;Petersen et al, 1996;Vuille-Dit-Bille et al, 2012;Jeter et al, 2013) and in animal models (Louin et al, 2007;Zheng et al, 2017;Taraskina et al, 2022). In a piglet TBI model, plasma levels of glycine, ornithine, and the nonproteinogenic amino acid taurine at 24 h post-injury correlated with central injury in a regression model (Hajiaghamemar et al, 2020).…”