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Recent research has shown there can be detrimental neurological effects ofshort- and long-term exposure to contact sports. In the present study,metabolomic profiling was combined with inflammatory miRNA quantification,computational behavior with virtual reality (VR) testing of motor control, andhead collision event monitoring to explore trans-omic and collision effects onhuman behavior across a season of players on a collegiate American footballteam. We integrated permutation-based statistics with mediation analyses totest complex, directional relationships between miRNAs, metabolites, and VRtask performance. Fourteen significant mediations (metabolite = mediator; miRNA= independent variable; VR score = dependent variable) were discovered atpreseason (N=6) and across season (N=8) with Sobel p-values less than or equalto 0.05 and with total effects at or exceeding 50%. The majority of mediationfindings involved long to medium chain fatty acids (2-HG, 8-HOA, UND, sebacate,suberate, and heptanoate). In parallel, TCA metabolites were found to besignificantly decreased at postseason relative to preseason. HAEs wereassociated with metabolomic measures and miRNA levels across-season. Together,these observations suggest a state of chronic HAE-induced neuroinflammation (asevidence by elevated miRNAs) and mitochondrial dysfunction (as observed byabnormal FAs and TCA metabolites) that together produce subtle changes inneurological function (as observed by impaired motor control behavior). Thesefindings point to a shift in mitochondrial metabolism, away from mitochondriafunction, consistent with other illnesses classified as mitochondrialdisorders, suggesting a plausible mechanism underlying HAEs in contact sportsand potential avenue for treatment intervention.

Metabolomic measures of altered energy metabolism mediate the relationship of inflammatory miRNAs to motor control in collegiate football athletes