Over the last decade, there has been rising interest in the topic of brain concussions and traumatic brain injury (TBI), especially for the purpose of understanding the long-term consequences and potential links to neurodegenerative diseases, multi-organ failure, mortality, and lifelong disability. In previous blogs, we have discussed various nutraceuticals and dietary approaches that are useful for brain injuries, including ketones, branched chain amino acids, omega-3 fatty acids, and zinc. In this blog, we will focus on the impact of brain injury on the gut-brain axis and intestinal health.
A great deal of functional medicine focuses on intestinal health as a foundational component of whole body health. Antibiotic use, poor dietary habits, environmental and food toxins, chronic stress, and biotoxins are among the most cited causes of intestinal dysfunction leading to a myriad of negative health outcomes. Unfortunately, brain injury (both concussions and TBIs) is another factor now known to damage the health of the gut, adding yet another layer of concern to an already serious health concern.
Various studies have cited gastrointestinal dysfunction as an outcome of TBI, but few have dissected the association. More specifically, TBI disrupts the intestinal barrier function by increasing intestinal permeability, which initiates the translocation of bacteria and bacterial products such as LPS, proteins, and toxins throughout the body.
TBI appears to act upon the transmembrane proteins responsible for creating the intracellular scaffolding necessary to maintain tight junctions between intestinal epithelial cells. In one study, the transmembrane proteins ZO-1 and occludin were measured after a TBI to determine intestinal permeability. TBI caused a significant increase in intestinal permeability within 6 hours after injury, as marked by the decreased expression of ZO-1 and occludin, by 49% and 73%, respectively. In another study, an increased ratio of ingested lactulose to mannitol in the urine following brain injury gave evidence to TBI-induced gaps in tight junctions. Glucose also reduces the expression of both ZO-1 and occluding, and a hyperglycemic state is characteristic of brain injury, offering a possible explanation for how ZO-1 and occludin are regulated during a TBI. The exact mechanism behind transmembrane protein regulation during brain injury is still unknown.
Other mechanisms triggered by brain injury enhance intestinal permeability. For example, TNF-α increases following TBI and also plays a key role in loosening tight junctions. In animal models, inhibiting TNF-α with the hormone ghrelin, vagal nerve stimulation, and glutamine reduces intestinal permeability and the pro-inflammatory response to brain injury.
The central nervous system also plays an important role in regulating the intestinal barrier through the gut-brain axis. The vagus nerve acts as the communication line between the brain and the gastrointestinal system, and helps to maintain gut homeostasis at various levels. Vagal stimulation is associated with “rest and digest” functions; however, brain injury shuts down the parasympathetic activity of the vagal nerve in favor of vigilant sympathetic activity. Inhibiting vagal activity reduces the production and secretion of various digestive enzymes and disturbs gut homeostasis, eventually leading to dysbiosis, SIBO, and a pro-inflammatory intestinal environment. In a study seeking to determine the impact of vagal nerve stimulation on the outcomes of TBI, the treatment significantly reduced intestinal permeability, prevented villi necrosis, and increased TNF-α, compared to the control group. This study supports the role of the vagal nerve as the conduit between TBI and gastrointestinal dysfunction. Further, low vagal tone has been a characteristic of IBS and IBD, indicating another connection between brain health and the gut.
Finally, brain injury also disturbs the gut microbiota, contributing to gastrointestinal dysfunction, systemic inflammation, dysimmunity, and other outcomes of TBI. In a study comparing the microbiota of those with head injury versus healthy controls, head injury significantly decreased the content of anaerobic groups including Bacteroides/Prevotella, Clostridium, Lactobacillus/Leuconostoc, and Bifidobacterium sp. The same study found a profound increase in the colonization of Escherichia coli.
Leaky gut, dysbiosis, SIBO, and gastrointestinal conditions are prevalent in functional medicine practices, but most likely, these conditions aren’t associated with brain injury. On the other hand, it is vital to address intestinal permeability and the gut microbiota when treating a brain injury as a way to prevent long-term health outcomes of brain injury, and to foster healing for the brain by reducing the inflammatory response that would originate from the gut.
By Nicole Spear, MS, CNS