Chronic spinal cord injury (SCI) results in an increased predisposition to various metabolic problems that can be exacerbated by consuming a diet rich in calories and saturated fat. In addition, gastrointestinal symptoms have been reported after SCI, including intestinal dysbiosis of the gut microbiome. The effects of both diet and SCI on the gut microbiome of adult male Long Evans rats euthanized 16 wk after injury were investigated. The rats were either thoracic spinal contused or received sham procedures. After 12 wk of either a low-fat or high-fat diet, cecal contents were analyzed, revealing significant microbial changes to every taxonomic level below the kingdom level. Shannon α diversity analyses demonstrated a significant difference in diversity between the groups based on the surgical condition of the rats. SCI produced a unique signature of changes in commensal bacteria that were significantly different than Sham. Specific changes in commensal bacteria as a result of diet manipulation had high fidelity with reports in the literature, such as Clostridia, Thiohalorhabdales, and Pseudomonadales. In addition, novel changes in commensal bacteria were identified that are unique dietary influences on SCI. Linear regression analysis on body fat and lean mass showed that a consequence of chronic SCI produces uncoupled associations between some commensal bacteria and body composition. In conclusion, despite tightly controlling the protein content and varying the carbohydrate and fat contents, Sham and SCI rats respond uniquely to diet. These data provide potential direction for therapeutic modulation of the microbiome to improve health and wellness following SCI.

Military Deployment to Southwest Asia and Afghanistan and exposure to toxic airborne particulates have been associated with an increased risk of developing respiratory disease, collectively termed deployment-related respiratory diseases (DRRDs). Our knowledge about how particulates mediate respiratory disease is limited, precluding the appropriate recognition or management. Central to this limitation is the lack of understanding of how exposures translate into dysregulated cell identity with dysregulated transcriptional programs. The small airway epithelium is involved in both the pathobiology of DRRD and fine particulate matter deposition. To characterize small airway epithelial cell epigenetic and transcriptional responses to Afghan desert particulate matter (APM) and investigate the functional interactions of transcription factors that mediate these responses, we applied two genomics assays, the assay for transposase accessible chromatin with sequencing (ATAC-seq) and Precision Run-on sequencing (PRO-seq). We identified activity changes in a series of transcriptional pathways as candidate regulators of susceptibility to subsequent insults, including signal-dependent pathways, such as loss of cytochrome P450 or P53/P63, and lineage-determining transcription factors, such as GRHL2 loss or TEAD3 activation. We further demonstrated that TEAD3 activation was unique to APM exposure despite similar inflammatory responses when compared with wood smoke particle exposure and that P53/P63 program loss was uniquely positioned at the intersection of signal-dependent and lineage-determining transcriptional programs. Our results establish the utility of an integrated genomics approach in characterizing responses to exposures and identifying genomic targets for the advanced investigation of the pathogenesis of DRRD.