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. 2021 Dec 24;12:800796. doi: 10.3389/fimmu.2021.800796

Table 2.

A summary of preclinical and human studies on the gut microbiota and traumatic brain injury.

Subjects Methods Key findings
Mahajan C, et al. (2021) (90) 101 patients –

  • All organisms belonged to the Proteobacteria phylum, especially Enterobacteriaceae forming the largest group after traumatic brain injury (TBI).

  • TBI is associated with widespread colonization with Proteobacteria as early as 48 hours after injury.
Hou Y, et al. (2021) (91) 24 patients vs. 10 controls; surgical brain injury (SBI) rat 16S rRNA sequencing & HPLC-MS

  • The abundances of Enterococcus, Parabacteroides, Akkermansia, and Lachnoclostridium were significantly increased, whereas the relative abundances of Bifidobacterium and Faecalibacterium were decreased in the patients with TBI.

  • Oral administration of brain protein combined with probiotics alleviated inflammatory gut damage by affecting tryptophan-related pathways.
Treangen TJ, et al. (2018) (92) controlled cortical impact (CCI) mice 16S rRNA (V3-V4) sequencing

  • At a high-level view, the abundances of Marvinbryantia and Clostridiales were significantly changed after TBI.

  • Lactobacillus gasseri, Ruminococcus flavefaciens, and Eubacterium ventriosum were decreased at the species level, while Eubacterium sulci and Marvinbryantia formatexigens and were increased after TBI.
Li H, et al. (2018) (93) weight-drop impact (WDI) mice –

  • Clostridium butyricum treatment improved neurological deficits, brain edema, neurodegeneration, and blood-brain barrier impairment.

  • Clostridium butyricum treatment increased tight junction proteins, p-Akt, and Bcl-2 and decreased expression of Bax.

  • Mice treated by Clostridium butyricum showed an increased intestinal Glucagon-like peptide 1(GLP-1) secretion and upregulated the expression of cerebral GLP-1 receptor.
Simon DW, et al. (2020) (89) CCI mice 16S rRNA (V4) sequencing

  • Mice receiving pretreatment of ampicillin, metronidazole, neomycin, and vancomycin(AMNV) before surgery increased CA1’s density of hippocampal neuronal and reduced Iba-1 positive cells at 72 h after TBI.

  • Mice pretreated by AMNV alleviated associative learning deficit and decreased lesion volume after TBI.
Angoa-Pérez M, et al. (2020) (94) WDI mice 16S rRNA (V4) sequencing

  • An early increase in microglial activation persisted from 0-day to 90-day post-injury, compounded by substantial increases in astrocyte reactivity and phosphorylated tau.

  • Few differences in the microbial community were observed in mice exposed to repetitive, mild TBI (rmTBI).

  • The progressive emergence of white matter damage and cognitive deficits following rmTBI was not associated with the altered gut microbiota.
Opeyemi OM, et al. (2021) (95) CCI mice model 16S rRNA (V4) sequencing & HPLC-MS

  • Bacteria from Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae families were depleted, while bacteria from the Verrucomicrobiaceae family were enriched.

  • Fecal SCFAs such as acetate were reduced at 7 days and 28 days following TBI; SCFAs administration improved spatial learning after TBI.
Du D, et al. (2021) (96) CCI rat 16S rRNA (V3-V4) sequencing & HPLC-MS

  • TBI induced significant changes in the gut microbiome, including the alpha- and beta-bacterial diversity and the microbiome composition at 8 days after TBI. Fecal microbiota transplantation (FMT) could rescue these changes and relieve neurological deficits after TBI.

  • Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI. At the same time, FMT decreased TMA levels in the feces and TMAO levels in the ipsilateral brain and serum.

  • FMT can restore gut microbiota dysbiosis and relieve neurological deficits, possibly through the TMA-TMAO-methionine sulfoxide reductase A (MsrA) signaling pathway after TBI.
You W, et al. (2021) (97) lateral fluid percussion injury mice model 16S rRNA (V3-V4) sequencing & HPLC-MS

  • The diversity of gut microbiota experienced a time-dependent change from 1 h to 7 days post-TBI.

  • The decreased levels of bile acids, especially secondary bile acids, were related to intestinal inflammation after TBI.

  • Staphylococcus and Lachnospiraceae may contribute to the bile acid metabolic changes.
Celorrio M, et al. (2021) (98) CCI mice PCR

  • Antibiotic-induced gut microbial dysbiosis significantly worsened neuronal loss after TBI.

  • Antibiotic exposure for 1 week after TBI decreased T lymphocyte infiltration, increased microglial pro-inflammatory markers, and reduced cortical infiltration of Ly6Chigh monocytes.

  • Gut microbiota dysbiosis was associated with increased hippocampal neuronal loss and fear memory response 3 months after TBI.

16S rRNA, 16S ribosomal RNA.

PCR, polymerase chain reaction.

HPLC-MS, high-performance liquid chromatography-mass spectrometry.