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Published on: June 11, 2017
Fecal microbial transplantation limits neural injury severity and functional deficits in a pediatric piglet traumatic
Madison M Fagan1,2,3, Christina B Welch3, Kelly M Scheulin1,2,3
1Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.
Insights
Fecal microbial transplant (FMT) in piglets with traumatic brain injury (TBI) reduced brain damage and improved gut health. This TBI treatment shows promise for better recovery and functional outcomes in children.
Area of Science:
- Neuroscience
- Gastroenterology
- Microbiology
Background:
- Pediatric traumatic brain injury (TBI) is a major cause of childhood death and disability.
- Gut-brain axis communication suggests microbial interventions may mitigate TBI secondary injury.
- Fecal microbial transplant (FMT) is a potential therapeutic strategy for TBI.
Purpose of the Study:
- To evaluate the efficacy of daily FMT in a pediatric piglet model of TBI.
- To assess FMT's impact on neural injury severity, gut dysbiosis, and functional recovery.
- To investigate FMT's effects on brain and gut tissues, and microbiome composition.
Main Methods:
- A translational pediatric piglet model with controlled cortical impact TBI.
- Random assignment to TBI + saline, TBI + FMT, or Sham + saline groups.
- Daily oral FMT or saline administration for 7 days, followed by MRI, histology, and microbiome analysis.
Main Results:
- FMT treatment reduced lesion and hemorrhage volumes post-TBI.
- Improved neuron and oligodendrocyte survival and restored ileum morphology were observed with FMT.
- FMT decreased gut dysbiosis, increased beneficial Lactobacilli, and improved motor function.
Conclusions:
- Daily FMT shows significant potential in limiting TBI-induced cellular and tissue damage.
- FMT treatment promotes gut microbiome restoration and enhances functional recovery post-TBI.
- This study provides novel evidence for FMT as a therapeutic approach for pediatric TBI.
Abstract:
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Due to bidirectional communication between the brain and gut microbial population, introduction of key gut bacteria may mitigate critical TBI-induced secondary injury cascades, thus lessening neural damage and improving functional outcomes. The objective of this study was to determine the efficacy of a daily fecal microbial transplant (FMT) to alleviate neural injury severity, prevent gut dysbiosis, and improve functional recovery post TBI in a translational pediatric piglet model. Male piglets at 4-weeks of age were randomly assigned to Sham + saline, TBI + saline, or TBI + FMT treatment groups. A moderate/severe TBI was induced by controlled cortical impact and Sham pigs underwent craniectomy surgery only. FMT or saline were administered by oral gavage daily for 7 days. MRI was performed 1 day (1D) and 7 days (7D) post TBI. Fecal and cecal samples were collected for 16S rRNA gene sequencing. Ipsilateral brain and ileum tissue samples were collected for histological assessment. Gait and behavior testing were conducted at multiple timepoints. MRI showed that FMT treated animals demonstrated decreased lesion volume and hemorrhage volume at 7D post TBI as compared to 1D post TBI. Histological analysis revealed improved neuron and oligodendrocyte survival and restored ileum tissue morphology at 7D post TBI in FMT treated animals. Microbiome analysis indicated decreased dysbiosis in FMT treated animals with an increase in multiple probiotic Lactobacilli species, associated with anti-inflammatory therapeutic effects, in the cecum of the FMT treated animals, while non-treated TBI animals showed an increase in pathogenic bacteria, associated with inflammation and disease such in feces. FMT mediated enhanced cellular and tissue recovery resulted in improved motor function including stride and step length and voluntary motor activity in FMT treated animals. Here we report for the first time in a highly translatable pediatric piglet TBI model, the potential of FMT treatment to significantly limit cellular and tissue damage leading to improved functional outcomes following a TBI.
