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Complex Feed-Forward and Feed-Back Mechanisms Underlie the Relationship Between Traumatic Brain Injury and the Gut–Microbiota–Brain Axis

Patterson, T. Tyler*; Nicholson, Susannah; Wallace, David; Hawryluk, Gregory W.J.§; Grandhi, Ramesh†,‡,§

doi: 10.1097/SHK.0000000000001278
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ABSTRACT Traumatic brain injury (TBI) contributes to nearly one in three injury-related deaths in the United States and accounts for a substantial public health burden and cost. The current literature reports that physiologic responses in the gastrointestinal system after TBI include, but are not limited to, epithelial barrier dysfunction, microbiota changes, and immunologic transformations. Recent evidence suggests gut alterations after TBI modify the homeostasis of the bidirectional gut–microbiota–brain axis, resulting in altered immune responses in the periphery and the brain. This cascade possibly contributes to impaired central nervous system (CNS) healing. Although attention to the gut–brain–microbiota axis has been increasing in the literature, the precise mechanisms underlying the changes observed after TBI remain unclear. The purpose of this review is to describe our current understanding regarding alterations to the gut–microbiota–brain axis after TBI, highlight the pathophysiologic changes involved, and evaluate how these variations modify healing in the CNS or even contribute to secondary injury. We also discuss current investigations into potential medical therapies directed at the gut–microbiota–brain axis, which might offer improved outcomes after TBI.

*Long School of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA

Division of Trauma and Emergency Surgery, Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Department of Neurosurgery, University of Texas Health Sciences Center at San Antonio, San Antonio, Texas, USA

§Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah, USA

Address reprint requests to Ramesh Grandhi, MD, University of Utah School of Medicine, Department of Neurosurgery, 175 North Medical Drive East, Salt Lake City, Utah 84132. E-mail: ramesh.grandhi@hsc.utah.edu

Received 3 August, 2018

Revised 29 August, 2018

Accepted 10 October, 2018

Financial and Material Support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflict of interest to report.

© 2019 by the Shock Society