The Beehive Theory: Role of microorganisms in late sequelae of traumatic brain injury and chronic traumatic encephalopathy

Abstract

Traumatic brain injury and chronic traumatic encephalopathy are both major health problems, well-publicized for the severe delayed effects attributed to them, including cognitive decline, psychiatric disorders, seizures, impaired motor function, and personality changes. For convenience, the two afflictions are considered together under the rubric traumatic brain injury. Despite the need for neuroprotective agents, no substances have shown efficacy in clinical studies. Thus, a deeper understanding of the neuropathological mechanism of such injury is still needed. Proposed here is a theory that microorganisms from within the brain and elsewhere in the body contribute to the long-term neurological deterioration characteristic of traumatic brain injury. The label, "The Beehive Theory", is drawn from the well-known fact that disturbing a tranquil beehive with a blow can cause a swarm of angry bees to exit their dwelling place and attack nearby humans. Similarly, an impact to the head can initiate dislocations and disruptions in the microbiota present in the brain and body. First, since the normal human brain is not sterile, but is host to a variety of microorganisms, blows to the skull may dislodge them from their accustomed local environments, in which they have been living in quiet equilibrium with neighboring brain cells. Deleterious substances may be released by the displaced microbes, including metabolic products and antigens. Second, upon impact commensal microbes already resident on surfaces of the nose, mouth, and eyes, and potentially harmful organisms from the environment, may gain access to the brain through the distal ends of the olfactory and optic nerves or even a disrupted blood-brain barrier. Third, microbes dwelling in more distant parts of the body may be propelled through the walls of local blood vessels into the bloodstream, and then leak out into damaged areas of the brain that have increased blood-brain barrier permeability. Fourth, the impact may cause dysbiosis in the gastrointestinal microbiome, thereby disrupting signaling via the gut-brain axis. Possible preventatives or therapeutics that would address the adverse contributions of microbes to the late sequelae of traumatic brain injury include anti-inflammatories, antibacterials, antivirals, and probiotics.