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. 2022 Apr 21;11(9):1409.
doi: 10.3390/cells11091409.

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

Anastasiia Taraskina  1 , Olga Ignatyeva  1 , Darya Lisovaya  1 , Mikhail Ivanov  1 , Lyudmila Ivanova  1 , Viktoriya Golovicheva  2 , Galina Baydakova  3 , Denis Silachev  2 , Vasiliy Popkov  2 , Tatyana Ivanets  4 , Daria Kashtanova  1 , Vladimir Yudin  1 , Valentin Makarov  1 , Ivan Abramov  1 , Mariya Lukashina  1 , Vera Rakova  1 , Anzhelika Zagainova  1 , Dmitry Zorov  2 , Egor Plotnikov  2 , Gennadiy Sukhikh  4 , Sergey Yudin  1
Affiliations

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

Anastasiia Taraskina et al. Cells. .

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.

Keywords: amino acids; complications of traumatic brain injury; gut microbiota; gut–brain axis; traumatic brain injury.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) LPT scores before (day 0) and on days 1, 3, and 7 after the TBI. Grouping was based on the observed dynamics of neurological recovery. (B) TBI-induced forelimb asymmetry measured with the Cylinder Test on day 7 after the TBI. (C) Representative T2-weighted MRIs of the coronal brain sections (0.8 mm thick, from rostral (left) towards caudal (right)), taken on day 7 after the TBI. (D) Morphometric analysis of the extent of the brain damage evaluated based on T2-weighted images.
Figure 2
Figure 2
(A) NSE levels in the pre-TBI (blue box) and post-TBI (orange box) serum samples of all rats. (B) NSE levels in the pre-TBI (left) and post-TBI (right) serum samples in Group 1 (blue box) and Group 2 (orange box).
Figure 3
Figure 3
Abundance of the main bacterial phyla before (samples 1 through 25) and after the TBI (samples 1i through 25i).
Figure 4
Figure 4
Phylogenetic tree diagram.
Figure 5
Figure 5
Significant post-TBI changes in the relative abundance of intestinal microorganisms. Note: The height of each bar depicts a fold change in the abundance of a specific microorganism: blue bars show increase and red bars show decrease in post-TBI abundance. Error bars denote CI95% for each change. We calculated the fold change in each microorganism as the mean of its fold changes across all samples before and after the TBI.
Figure 6
Figure 6
(A) Support-vector-machine analysis of the discrimination between the pre-and post-TBI samples based on PC1 and PC2. (B) Distribution of the distances to the separating hyperplane in the pre-and post-TBI samples.
Figure 7
Figure 7
Shannon indices before (day 0) and after the TBI (day 7).
Figure 8
Figure 8
NMDS of beta-diversity in the samples. Ellipsoids correspond to 95% confidence intervals. Note: The purple and blue ellipsoids show the microbiome before and after the TBI, respectively.
Figure 9
Figure 9
Amino acid levels in blood serum before and on days 3 and 7 after the TBI.
Figure 10
Figure 10
Fold changes in amino acid levels (A) before and on day 7 after the TBI; (B) before and on day 3 after the TBI; (C) on days 3 and 7 after the TBI. Significant results are shown in red.
Figure 11
Figure 11
Fold changes in the relative abundance of the post-TBI gut microbiota species in Group 1 (blue) and Group 2 (red).
Figure 12
Figure 12
Shannon diversity indices of the pre-TBI gut microbiota in Group 1 and Group 2.
Figure 13
Figure 13
Fold changes in pre-TBI (day 0) amino acid levels in Groups 1 and 2. Significant results are presented in red.
Figure 14
Figure 14
Fold changes in post-TBI amino acid levels in Groups 1 and 2 between days 3 and 7. Significant results are presented in red.
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