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

Donglin Du,Zhengqiang Wei,Jianjun Zhong,Xiaochuan Sun,Wei Tang,Chao Zhou,Zhijian Huang,Luciana Mosca

doi:10.1155/2021/5816837

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.

Highlights

Traumatic brain injury (TBI) is a global public health concern, which affects approximately 10 million people each year worldwide [1] and is the primary cause of death in individuals under the age of 45 years [2]
At 8 days after TBI, there were no differences in the sequence reads among each group (Figure 1(a)) and the number of operational taxonomic units (OTUs) on TBI and TBI+saline groups were similar but significantly less than the sham and TBI+fecal microbiota transplantation (FMT) groups, indicating that the total number of taxonomic units representing microbial species had changed after 8 days post-TBI (Figure 1(b))
There were no differences in the value of Ace, Chao, and Coverage indices in the TBI group when compared with the TBI+saline group

Summary

Introduction

Traumatic brain injury (TBI) is a global public health concern, which affects approximately 10 million people each year worldwide [1] and is the primary cause of death in individuals under the age of 45 years [2]. An increasing number of studies have shown that the gut microbiota can regulate development of the CNS and brain function [5,6,7]. The gut microbiome structure and composition are altered in neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, autism, schizophrenia, and depression. These microbiome changes can contribute to the development of disease pathology [8,9,10,11,12].

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