Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury

Abstract

Background. Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats. Methods. A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain. Results. TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, 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, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI. Conclusions. FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

“…Interestingly, vagal stimulation reduced gut barrier permeability after TBI, mediated by the suppression of TNF-a release (106). Recently, it has been demonstrated that FMT can restore gut microbiota dysbiosis following TBI and ameliorate neurological deficits, mediated by the TMA-TMAO-MsrA signaling pathway (96).…”

Protective role of wogonin following traumatic brain injury by reducing oxidative stress and apoptosis via the PI3K/Nrf2/HO‑1 pathway

“…The direct cause of tissue damage following TBI is the increase of local oxygen free radicals and the occurrence of stress oxidation reaction. Among them, ROS and MDA are directly involved in brain damage and excessive release of excitatory neurotransmitters ( 30 ). Following TBI, the levels of ROS and MDA rise sharply, while the activities of biological enzymes that scavenger oxygen free radicals, such as SOD and CAT, remain basically unchanged ( 31 , 32 ).…”

Gastrointestinal Microbiome and Neurologic Injury

“…Gut-dysbiosis-induced neuroinflammation seems to be at least partially mediated by microglia and astrocytes, which have also been shown to be regulated by enteric metabolites [ 54 , 61 , 64 ]. Restoration of healthy microbiota can interrupt this process and improve neurological deficits after TBI [ 76 ]. Consistent with the general model of the gut–brain axis, SCFA metabolism seems to be a critical element of TBI-induced gut dysbiosis.…”