Abstract
Current efficacious treatments for traumatic brain injury (TBI) are lacking. Establishment of a protective gut microbiota population offers a compelling therapeutic avenue, as brain injury induces disruptions in the composition of the gut microbiota, i.e., gut dysbiosis, which has been shown to contribute to TBI-related neuropathology and impaired behavioral outcomes. The gut microbiome is involved in the modulation of a multitude of cellular and molecular processes fundamental to the progression of TBI-induced pathologies including neuroinflammation, blood brain barrier permeability, immune system response, microglial activation, and mitochondrial dysfunction, as well as intestinal motility and permeability. Additionally, gut dysbiosis further aggravates behavioral impairments in animal models of TBI and spinal cord injury, as well as negatively affects health outcomes in murine stroke models. Recent studies indicate that microbiota transplants and probiotics ameliorate neuroanatomical damage and functional impairments in animal models of stroke and spinal cord injury. In addition, probiotics have been shown to reduce the rate of infection and time spent in intensive care of hospitalized patients suffering from brain trauma. Perturbations in the composition of the gut microbiota and its metabolite profile may also serve as potential diagnostic and theragnostic biomarkers for injury severity and progression. This review aims to address the etiological role of the gut microbiome in the biochemical, neuroanatomical, and behavioral/cognitive consequences of TBI, as well as explore the potential of gut microbiome manipulation in the form of probiotics as an effective therapeutic to ameliorate TBI-induced pathology and symptoms.
Highlights
Brain Trauma Neuroprotection Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, United States
This review aims to address the etiological role of the gut microbiome in the biochemical, neuroanatomical, and behavioral/cognitive consequences of traumatic brain injury (TBI), as well as explore the potential of gut microbiome manipulation in the form of probiotics as an effective therapeutic to ameliorate TBI-induced pathology and symptoms
Probiotics consisting of lactobacilli, bifidobacteria, and other butyrate-producing gut bacteria appear most beneficial, providing a eubiotic therapy that enhances MICROBIOTA-GUT-BRAIN AXIS (MGBA) function through their anti-inflammatory and positive mitochondrial energetic properties
Summary
Traumatic brain injury (TBI) is a major cause of death and disability in the United States and represents one of the most prevalent injury types sustained by the worldwide population [1]. The activity and composition of this microbial population is involved in a surprising number of biological processes, including homeostasis of the central nervous system (CNS) [24,25,26] This relationship is referred to as the microbiota-gut-brain axis (MGBA) [27], with communication between the gut microbiota and the CNS occurring through a neuro-endocrino-immunological network [28]. It is difficult to prove causation and directionality when discussing gut microbiome changes observed in human neuropsychiatric and neurodegenerative conditions [57] For these reasons, rodents are commonly used when investigating the MGBA as they [1] possess similar, but not identical, core intestinal bacterial populations to humans [58, 59] and [2] can be maintained “germ free” (devoid of gut microbiota) or gnotobiotic (gut microbiota of known composition). Among other research findings [as reviewed by [67]], this has led some researchers to suggest “psychobiotics” as a new therapeutic approach for neurological and neuropsychiatric illnesses [68, 69]
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