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. 2022 May;17(5):1007-1008.
doi: 10.4103/1673-5374.324839.

Gut-brain axis in traumatic brain injury: impact on neuroinflammation

Marta Celorrio  1 , Stuart H Friess  1
Affiliations

Gut-brain axis in traumatic brain injury: impact on neuroinflammation

Marta Celorrio et al. Neural Regen Res. 2022 May.
No abstract available

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Conflict of interest statement

None

Figures

Figure 1
Figure 1
Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis. (A) Experimental design for the murine model of microbial dysbiosis after traumatic brain injury (TBI). Adult male C57BL/6J mice underwent controlled cortical impact (CCI) or sham surgery, and were immediately randomized to broad-spectrum antibiotics in the drinking water (vancomycin, neomycin-sulfate, ampicillin, metronidazole (VNAM)) and Kool-Aid or Kool-Aid alone. After 1 week, all mice resumed normal drinking water. Mice were sacrificed at 3 days for flow cytometry, 7 days for flow cytometry and histopathological analysis, 1 month for flow cytometry and at 3 months post-injury for fear conditioning testing and histopathological analysis. (B) Temporal innate and adaptive immune response in TBI with and without microbial dysbiosis. In injured mice with a normal microbiota (TBI Kool-Aid), monocytes infiltrated the brain constituting the innate immune response (3 days post-injury) followed by activation of microglia with a peak at 7 days post-injury. The innate immune response makes a crucial contribution to the activation of adaptive immunity with T cell (T effector and T reg) infiltration into damaged tissue. In the case of injured mice with microbial dysbiosis, infiltration of the monocytes and T cells was suppressed with increased microglial activation at 3 months. (C) Summary of major findings from Celorrio et al. (2021) and potential mechanistic links in TBI Kool-Aid (top) and TBI VNAM (bottom) mice. The number of microglia in the injured hippocampus did not differ between TBI Kool-Aid and TBI VNAM mice; however, microbial dysbiosis induced an increase of pro-inflammatory microglial surface markers (TLR4 and MHCII) with changes in microglial morphology toward an amoeboid shape. Reduction in bacterial metabolites produced by gut bacteria after VNAM exposure may be responsible for the modulation in microglial morphology and activation which may alter cytokine signaling and T cells populations that are recruited to the injury site. Reduced monocyte infiltration associated with gut microbial dysbiosis may also play a role in microglial activation and T cell infiltration. Amoeboid microglia may liberate pro-inflammatory cytokines such as IL-12 and IL-6, which may modulate the T effector cell response toward Th1/Th17 and away from a Th2/T reg neuroprotective phenotype. These neuroinflammatory changes were associated with reduced neurogenesis in the dentate gyrus (DG), increased neuronal degeneration in the CA3 region of the hippocampus, and altered fear memory response in TBI VNAM mice. BBB: Blood-brain barrier; IL: interleukin; MHCII: MHC class II; TLR4: Toll-like receptor 4.
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