Microbiome alteration: Potential signature to discriminate features associated with TBI vs. psychological stress

Abstract

Traumatic brain injury (TBI) is a major source of morbidity and mortality within current war zones. On the other hand, psychological disorders such as post‐traumatic stress disorder (PTSD) are emerging as the major career limiting factors for combat soldiers. A knowledge‐driven unbiased panel of signatures to discriminate between psychological stress and TBI is essential for designing precise care management. Towards this objective, the present study was conducted in the fecal microbiome in rats maintained on diets with varied polyunsaturated fat compositions, intended to nutritionally influence their vulnerabilities to these insults. Emerging knowledge has suggested a role of TBI and psychological stress in alterations of the gut microbiota architecture leading to bacterial translocation. However, the biological importance of these alterations in traumatic injury or stress is not well understood. To determine how the shift in the microbiome population is coordinated with the traumatic injury and stress responses, two animal models were chosen. A closed‐head TBI model consisting of blast overpressure (BOP) wave exposure coupled with a weight drop concussion (Marmarou method) was used on a group of rats selected to receive TBI. The anesthetized animals were subjected once to BOP (18 psi) inside an Advanced Blast Simulator (ABS), which was then immediately followed by dropping a 500‐gram metal weight from 125 cm above onto a stainless steel disc affixed to the rat's skull midway between lambda and bregma. Shams received anesthesia. In parallel, an independent group of rats was subjected to an underwater trauma (UWT) stressor model that consisted of 30s of swimming and habituation, followed by 30s of forced whole body immersion. Shams received 1min of free swimming. Existing literature and our data shows that UWT elicits PTSD‐like features in rats (e.g. prolonged “anxiety” behaviors). Before TBI or UWT, animals were maintained for 6 weeks and continued thereafter on three different diets: (i) Standard house chow; (ii) Custom chow enriched with 1% of calories as Linoleic acid (LA) and (iii) Custom chow enriched with 8% LA. Unlike the house chow, the two custom diets contained no long chain ω‐3 polyunsaturated fatty acids (PUFAs) to offset their high LA (ω‐6 PUFA) content.The fecal bacterial populations were characterized by identification of 16S ribosomal RNA sequencing. Principal Coordinate Analysis (PCoA) showed clear separation between phylogenetic profiles linked to TBI and UWT, respectively; however, only TBI showed some distinctions from their corresponding shams. Within each group, TBI or UWT, the phylogenetic profile linked to rodents fed on house chow showed diversion from the other two diet groups. No significant separation was observed between rats fed on either the 1% or 8% LA enriched diets that were absent in long chain omega‐3 PUFAs.We will further investigate genomic alterations within tissues that can be attributed to the different traumatic injury and stress factors and diet compositions. Final deliverable will articulate the role of the gut‐brain axis in different traumatic injury and stress conditions while also defining how fecal microbial signatures can discriminate between the features linked to TBI and psychological stress.Support or Funding InformationMOMRPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.