Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner

Abstract

The microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophage, fungi, protozoa and viruses) that colonize the human body, and alterations have been associated with a number of disease states. Changes in gut commensals can influence the neurologic system via the brain-gut axis, and systemic insults such as trauma or traumatic brain injury (TBI) may alter the gut microbiome. The objective of this study was to evaluate the gut microbiome in a pre-clinical TBI cortical impact model. Male rats underwent craniotomy and randomized to a sham group (n = 4), or a moderate TBI (n = 10) using a pneumatic impactor. MRI and behavioral assessments were performed pre-TBI and on days 2, 7 and 14 days thereafter. Microbiome composition was determined with 16 s rRNA sequencing from fecal sample DNA pre-TBI and 2 hrs, 1, 3, and 7 days afterwards. Alpha- and β- bacterial diversity, as well as organizational taxonomic units (OTUs) were determined. Significant changes in the gut microbiome were evident as early as 2 hrs after TBI as compared to pre-injured samples and sham rats. While there were varying trends among the phylogenetic families across time, some changes persisted through 7 days in the absence of therapeutic intervention. While large structural lesions and behavioral deficits were apparent post-TBI, there were modest but significant decreases in α-diversity. Moreover, both changes in representative phyla and α-diversity measures were significantly correlated with MRI-determined lesion volume. These results suggest that changes in the microbiome may represent a novel biomarker to stage TBI severity and predict functional outcome.

Association of gut microbiota with cerebral cortex and cerebrovascular abnormality in human mild traumatic brain injury

“…Accordingly, we selected PID 2-5 as the time of our fecal sample analysis in patients. Rodent studies also found obviously decreased α-diversity of gut microbiota in animals exposed to TBI 49,50 , which is in contrast to our findings indicating greater α-diversity in patients. Moreover, more differentially enriched phyla, families and genera were found in the present study of human TBI than those identified by the rodent model of TBI.…”

“…These discrepancies in findings can be attributed to the intrinsic differences in gut microbiota and host physiology between humans and animals, as well as to the varied exposure factor (mild vs. moderate-severe TBI) or sampling location (feces vs. cecum/jejunum). Some consistent findings also existed between our human study and previous animal studies, for example, decreased Firmicutes and Deferribacteres and increased Bacteroidetes and Proteobacteria 49,50 in phylum, increased Bioinformatic analysis. All analyses were completed on the Biomarker BioCloud platform (www.biocloud.org) as described in ref.…”

“…Mild TBI significantly altered the abundances of 7 in 14 phyla, 10 in 22 classes, 26 in 44 orders, 35 in 76 families, and 61 in 205 genera in the gut with FDR < 0.05. By then, a total of 4 published animal studies [48][49][50][51] investigated gut bacteria after TBI and reported that altered gut microbiota emerged at PID 1 and remained significant at PID 3, and gut dysbiosis recovered at PID 7. Accordingly, we selected PID 2-5 as the time of our fecal sample analysis in patients.…”

Approaches to Monitor Circuit Disruption after Traumatic Brain Injury: Frontiers in Preclinical Research

“…Gastrointestinal disorders consequently disrupt the microbiota (gut bacteria) and accumulating data suggesting that the microbiome is the key regulator of the bidirectional gut-brain axis to influence brain function, behavior and host physiology [232]. Preclinical reports have shown microbiota dysbiosis after TBI [233,234]. Yet the link to PCSs has not studied.…”

Spinal cord injury and the human microbiome: beyond the brain–gut axis

“…Moreover, the changes observed in the bacterial diversity correlated with post-TBI, MRI-determined lesion volume and loss of behavioral function in the animal model. 28 Two laboratories have independently demonstrated the brain-gut pathway after stroke, which affects gut dysbiosis, neuroinflammatory injury response, and functional outcomes. 4, 39 Singh et al showed germ-free mice recolonized with poststroke microbiota had larger stroke lesions.…”