Gut Reaction: How your microbiome responds to traumatic brain injury

Illustration by Jennifer Broza

The fragility of our brains becomes painfully apparent when we consider the thousands of deaths each year resulting from motor collisions, falls, violence, and athletic injuries (11). In the United States, approximately 1.7 million people every year sustain traumatic brain injuries (TBI), which are characterized by a penetrating blow to the head. TBI’s wide spectrum of outcomes can range from temporary loss of consciousness to comas or even death: TBI causes about 50,000 deaths every year, a shocking fifty percent of them within the first couple hours after injury (12). 

As of now, no medication exists that can limit or reverse the damage directly due to the moment of trauma such as nerve or structural damage. For patients in the intensive care unit (ICU), treatment strives to prevent secondary insults, after-the-fact effects that result in further neurological damage. For example, physicians often adjust blood pressure levels, which can have myriad effects benefitting the patient, including raising blood oxygenation levels and decreasing blood glucose (12).

Within the past couple of years as interdisciplinary medicine has grown more prominent, a new path of potential TBI treatments has arisen out of gut microbiome research. These studies are done on the bacteria and other microbes located in the digestive tract. Growing curiosity about gut microbiota—the community of microorganisms in the microbiome—emerged less than twenty years ago, catalyzed by advances in microbe DNA sequencing (5). However, for almost 150 years, we have known that the brain and gut interact with one another through the enteric nervous system (ENS), a collection of nerve cells that line the inside of the gastrointestinal tract (13). The ENS communicates directly with the central nervous system through a four-lane interstate, formally known as the gut-brain axis (1). As scientists have explored the intersections between gut microbiota and psychiatry, geriatrics, and neurodegenerative medicine, discoveries have also coupled microbiome health to conditions like Alzheimer’s, Parkinson’s, schizophrenia, and autism (5). Distress in one system can induce a perceptible reaction in the other, forcing us to reconsider everything from what we put in our mouths each day to how maintaining gut health boost outcomes in head trauma patients (1). 

While our knowledge of the mechanisms and the exact role of the brain-gut axis—either to provoke inflammation or to protect neurons—is still developing, the correlation between TBI and damage to the gut’s bacterial communities is manifest. Recent studies by Dr. Caroline Zhu and her team at the University of Texas have shown that within two hours after moderate TBI, the microbiota undergoes considerable change, sharply dropping in diversity and altering in composition (7). This gut dysbiosis (an imbalance of microbes in the gut) can prove harmful as the body’s myriad microbes perform a multitude of roles: stimulating the immune system, digeston, regulating intestinal permeability, and producing specific proteins. As Zhu’s team describes, the secondary insults from TBI—including hemorrhage, reduced blood flow, and neuron death—can translate to changes in the gut through the activation of protein cascades and immune cells, ultimately aggravating inflammation in the brain (7). 

To counter microbe dysfunction in patients with TBI, researchers have generated an array of treatment options. Several approaches aim to actively rebuild the microbiota diversity, such as fecal microbiota transplantation. While typically used for antibiotic therapy complications, transplantation, in essence, transfers a healthy donor’s feces into the gastrointestinal tracts of TBI patients whose gut diversity had been compromised (7). Similarly, probiotics—microorganisms included in fermented food products, dietary and cosmetics—maintain the microbial community and influence immune response; specifically, they alter cytokine levels to control inflammation (9). Another treatment involves stimulating the vagus nerve, a cranial nerve linked to the digestive system that stimulates the gut’s nerve cells and controls channels in the intestine (7). Nutritional health interventions, such as targeted diets, also counteract gut dysbiosis. In TBI animal models, a high-ketone ketogenic diet decreases bruising, swelling, and cell apoptosis—a form of cellular programmed death—in the cerebral cortex (10). In developing these treatments, researchers hope to improve outcomes in patients with TBI by decreasing morbidity and mitigating the harmful effects of dysbiosis. 

The unfolding research has yielded encouraging results for TBI patients worldwide. Through further study of the gut-brain axis, we should be capable of diminishing mortality rates and post-recovery complications by enhancing therapeutic targets for neuroprotection. Dr. Stuart Friess, an associate professor in pediatric critical care at Washington University School of Medicine and active investigator of delayed secondary insults after TBI, sees great potential in exploring gut microbiota’s influence on TBI, tissue repair, and the following neurological outcomes. “This knowledge gap is of paramount clinical significance as TBI patients are highly susceptible to alterations in gut microbiota due to frequent antibiotic administration, prolonged hospitalization and autonomic dysfunction,” Friess commented. “Modulation of the gut microbiome may be a new avenue for neuroprotective or neurorestorative therapeutics in the care of patients with TBI.” As with all translational research, we wonder what implications the gut microbiome-TBI relationship might have on patient care. If gut dysbiosis affects the state of the brain, do antibiotics given to treat other symptoms also play a role in decreasing microbe diversity and thus slow recovery? How could patient care for individuals with TBI in the ICU evolve? 

As its growing salience in public health discourse becomes undeniable, investigation into the gut dysbiosis following TBI could prove extremely valuable. While research is currently limited to animal models, this intersection of digestive health and neuroscience could demonstrate much potential in improving critical care outcomes. By grasping the mechanistic intricacies of the communication between microbiome and brain, we will broaden both the treatment possibilities and futures of individuals suffering from TBI.

Edited by: Morgan Leff

Illustrated by: Jennifer Broza

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