Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension, hypoxia, intracranial hypertension, and detrimental inflammation. However, the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems. Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease. A critical component of this axis is the microorganisms of the gut known as the gut microbiome. Changes in gut microbial populations in the setting of central nervous system disease, including traumatic brain injury, have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care. In this review article, we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury. We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.