Abstract
Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions. These systemic manifestations suggest possible involvement of the gut microbiota in head injury outcomes. Although gut dysbiosis after single, severe TBI has been documented, the majority of head injuries are mild, such as those that occur in athletes and military personnel exposed to repetitive head impacts. Therefore, it is important to determine if repetitive, mild TBI (rmTBI) will also disrupt the gut microbiota. Male mice were exposed to mild head impacts daily for 20 days and assessed for cognitive behavior, neuropathology and disruptions in the gut microbiota at 0, 45 or 90 days after injury. Deficits in recognition memory were evident at the late post-injury points. Brains show an early increase in microglial activation at the 0-day time point that persisted until 90 days post-injury. This was compounded by substantial increases in astrocyte reactivity and phosphorylated tau at the 90-day time point. In contrast, changes in the microbial community were minor and transient, and very few differences were observed in mice exposed to rmTBI compared to controls. While the progressive emergence of white matter damage and cognitive alterations after rmTBI resembles the alterations observed in athletes and military personnel exposed to rmTBI, these changes could not be linked to systematic modifications in the gut microbiota.
Highlights
Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions
The results from the present studies lead to the conclusion that rmTBI causes recognition memory impairments at late time points as well as progressive damage in the optic tract
Increases in astrocyte reactivity are evident from the intermediate time point post-injury until the late point
Summary
Traumatic brain injury (TBI) is often accompanied by gastrointestinal and metabolic disruptions These systemic manifestations suggest possible involvement of the gut microbiota in head injury outcomes. The metabolic alterations that accompany more severe TBI often require enhanced nutritional support to counter the “resistance to renutrition” that is seen in this and numerous other hypercatabolic situations[20,21] Taken together, these latter complications of TBI suggest involvement of the gut microbiota. In light of the fact that the majority of military and sports-related TBIs are repeated and mild in nature, and considering that the fecal microbiota is altered for more than 20 years in humans after TBI30, we have evaluated the gut microbiota response to rmTBI involving 20 mild head impacts and longer survival times post-injury. The results show a progressive emergence of white matter damage, cognitive deterioration and a mild, transient gut dysbiosis
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