Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury

• Published in: The Journal of clinical investigation Vol. 131; no. 12
• Main Authors: Hanscom, Marie, Loane, David J, Shea-Donohue, Terez
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.06.2021
• Subjects: Animals; Brain; Brain - metabolism; Brain - microbiology; Brain - pathology; Brain Injuries, Traumatic - metabolism; Brain Injuries, Traumatic - microbiology; Brain Injuries, Traumatic - pathology; Cellular signal transduction; Central nervous system; Development and progression; Dysbiosis; Gastrointestinal Microbiome; Gastrointestinal system; Health aspects; Humans; Inflammation; Inflammation - metabolism; Inflammation - microbiology; Inflammation - pathology; Injuries; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Neurological research; Physiological aspects; Review Series; United States
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI143777

Traumatic brain injury (TBI) is a chronic and progressive disease, and management requires an understanding of both the primary neurological injury and the secondary sequelae that affect peripheral organs, including the gastrointestinal (GI) tract. The brain-gut axis is composed of bidirectional pathways through which TBI-induced neuroinflammation and neurodegeneration impact gut function. The resulting TBI-induced dysautonomia and systemic inflammation contribute to the secondary GI events, including dysmotility and increased mucosal permeability. These effects shape, and are shaped by, changes in microbiota composition and activation of resident and recruited immune cells. Microbial products and immune cell mediators in turn modulate brain-gut activity. Importantly, secondary enteric inflammatory challenges prolong systemic inflammation and worsen TBI-induced neuropathology and neurobehavioral deficits. The importance of brain-gut communication in maintaining GI homeostasis highlights it as a viable therapeutic target for TBI. Currently, treatments directed toward dysautonomia, dysbiosis, and/or systemic inflammation offer the most promise.