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Abstract
Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.
Keywords
brain-gut-microbial axis
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fecal microbiota transplantations
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microbes
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nervous system
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traumatic brain injury
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Jie Yu, Yun-Xin Chen, Jin-Wei Wang, Hai-Tao Wu.
Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis.
Ibrain, 2024, 10(4): 477-487 DOI:10.1002/ibra.12153
| [1] |
Robinson CP. Moderate and severe traumatic brain injury. Continuum. 2021;27(5):1278-1300.
|
| [2] |
Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury. Med Clin North Am. 2020;104(2):213-238.
|
| [3] |
Iftikhar PM, Anwar A, Saleem S, Nasir S, Inayat A. Traumatic brain injury causing intestinal dysfunction: a review. J Clin Neurosci. 2020;79:237-240.
|
| [4] |
Pan P, Song Y, Du X, et al. Intestinal barrier dysfunction following traumatic brain injury. Neurol Sci. 2019;40(6):1105-1110.
|
| [5] |
Sundman MH, Chen N, Subbian V, Chou Y. The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. Brain Behav Immun. 2017;66:31-44.
|
| [6] |
Ohbe H, Jo T, Matsui H, Fushimi K, Yasunaga H. Early enteral nutrition in patients with severe traumatic brain injury: a propensity score-matched analysis using a nationwide inpatient database in Japan. Am J Clin Nutr. 2020;111(2):378-384.
|
| [7] |
Brenner LA, Stearns-Yoder KA, Hoffberg AS, et al. Growing literature but limited evidence: a systematic review regarding prebiotic and probiotic interventions for those with traumatic brain injury and/or posttraumatic stress disorder. Brain Behav Immun. 2017;65:57-67.
|
| [8] |
Peeters W, van den Brande R, Polinder S, et al. Epidemiology of traumatic brain injury in Europe. Acta Neurochir. 2015;157(10):1683-1696.
|
| [9] |
Cheng P, Yin P, Ning P, et al. Trends in traumatic brain injury mortality in China, 2006-2013: a population-based longitudinal study. PLoS Med. 2017;14(7):e1002332.
|
| [10] |
Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol. 2021;357:577619.
|
| [11] |
Kaur P, Sharma S. Recent advances in pathophysiology of traumatic brain injury. Curr Neuropharmacol. 2018;16(8):1224-1238.
|
| [12] |
Cash A, Theus MH. Mechanisms of blood-brain barrier dysfunction in traumatic brain injury. Int J Mol Sci. 2020;21(9):3344.
|
| [13] |
Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020;17(1):69.
|
| [14] |
Hanscom M, Loane DJ, Shea-Donohue T. Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury. J Clin Invest. 2021;131(12):e143777.
|
| [15] |
Ferrara M, Bertozzi G, Zanza C, et al. Traumatic brain injury and gut brain axis: the disruption of an alliance. Rev Recent Clin Trials. 2022;17(4):268-279.
|
| [16] |
Patterson TT, Nicholson S, Wallace D, Hawryluk GWJ, Grandhi R. Complex feed-forward and feedback mechanisms underlie the relationship between traumatic brain injury and the gut-microbiota-brain axis. Shock. 2019;52(3):318-325.
|
| [17] |
Osadchiy V, Martin CR, Mayer EA. The gut-brain axis and the microbiome: mechanisms and clinical implications. Clin Gastroenterol Hepatol. 2019;17(2):322-332.
|
| [18] |
Mayer EA, Tillisch K, Gupta A. Gut/brain axis and the microbiota. J Clin Invest. 2015;125(3):926-938.
|
| [19] |
Margolis KG, Cryan JF, Mayer EA. The microbiota-gut-brain axis: from motility to mood. Gastroenterology. 2021;160(5):1486-1501.
|
| [20] |
Cannon AR, Anderson LJ, Galicia K, et al. Traumatic brain injury-induced inflammation and gastrointestinal motility dysfunction. Shock. 2023;59(4):621-626.
|
| [21] |
Ma Y, Liu T, Fu J, et al. Lactobacillus acidophilus exerts neuroprotective effects in mice with traumatic brain injury. J Nutr. 2019;149(9):1543-1552.
|
| [22] |
Lu K, Mahbub R, Fox JG. Xenobiotics: interaction with the intestinal microflora. ILAR J. 2015;56(2):218-227.
|
| [23] |
Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836.
|
| [24] |
Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019;76(3):473-493.
|
| [25] |
Kåhrström CT, Pariente N, Weiss U. Intestinal microbiota in health and disease. Nature. 2016;535(7610):47.
|
| [26] |
Nicholson SE, Watts LT, Burmeister DM, et al. Moderate traumatic brain injury alters the gastrointestinal microbiome in a time-dependent manner. Shock. 2019;52(2):240-248.
|
| [27] |
Treangen TJ, Wagner J, Burns MP, Villapol S. Traumatic brain injury in mice induces acute bacterial dysbiosis within the fecal microbiome. Front Immunol. 2018;9:2757.
|
| [28] |
Urban RJ, Pyles RB, Stewart CJ, et al. Altered fecal microbiome years after traumatic brain injury. J Neurotrauma. 2020;37(8):1037-1051.
|
| [29] |
Taraskina A, Ignatyeva O, Lisovaya D, et al. Effects of traumatic brain injury on the gut microbiota composition and serum amino acid profile in rats. Cells. 2022;11(9):1409.
|
| [30] |
Tyler Patterson T, Grandhi R. Gut microbiota and neurologic diseases and injuries. Adv Exp Med Biol. 2020;1238:73-91.
|
| [31] |
Celorrio M, Abellanas MA, Rhodes J, et al. Gut microbial dysbiosis after traumatic brain injury modulates the immune response and impairs neurogenesis. Acta Neuropathol Commun. 2021.9(1):40.
|
| [32] |
Li H, Sun J, Du J, et al. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis. Neurogastroenterol Motil. 2018;30(5):e13260.
|
| [33] |
O’Riordan KJ, Collins MK, Moloney GM, et al. Short chain fatty acids: microbial metabolites for gut-brain axis signalling. Mol Cell Endocrinol. 2022;546:111572.
|
| [34] |
Wenzel TJ, Gates EJ, Ranger AL, Klegeris A. Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells. Mol Cell Neurosci. 2020;105:103493.
|
| [35] |
Swer NM, Venkidesh BS, Murali TS, Mumbrekar KD. Gut microbiota-derived metabolites and their importance in neurological disorders. Mol Biol Rep. 2023;50(2):1663-1675.
|
| [36] |
Agirman G, Yu KB, Hsiao EY. Signaling inflammation across the gut-brain axis. Science. 2021;374(6571):1087-1092.
|
| [37] |
Petrella C, Strimpakos G, Torcinaro A, et al. Proneurogenic and neuroprotective effect of a multi strain probiotic mixture in a mouse model of acute inflammation: involvement of the gut-brain axis. Pharmacol Res. 2021;172:105795.
|
| [38] |
Killen MJ, Giorgi-Coll S, Helmy A, Hutchinson PJ, Carpenter KL. Metabolism and inflammation: implications for traumatic brain injury therapeutics. Expert Rev Neurother. 2019;19(3):227-242.
|
| [39] |
Royes LFF, Gomez-Pinilla F. Making sense of gut feelings in the traumatic brain injury pathogenesis. Neurosci Biobehav Rev. 2019;102:345-361.
|
| [40] |
Shields DC, Haque A, Banik NL. Neuroinflammatory responses of microglia in central nervous system trauma. J Cereb Blood Flow Metab. 2020;40(1_suppl):S25-S33.
|
| [41] |
Dabrowski W, Siwicka-Gieroba D, Kotfis K, et al. The brain-gut axis-where are we now and how can we modulate these connections. Curr Neuropharmacol. 2021;19(8):1164-1177.
|
| [42] |
Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2016;173(4):649-665.
|
| [43] |
Witcher KG, Bray CE, Chunchai T, et al. Traumatic brain injury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia. J Neurosci. 2021;41(7):1597-1616.
|
| [44] |
Hegdekar N, Sarkar C, Bustos S, et al. Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes. Autophagy. 2023;19(7):2026-2044.
|
| [45] |
Mira RG, Lira M, Cerpa W. Traumatic brain injury: mechanisms of glial response. Front Physiol. 2021;12:740939.
|
| [46] |
Muller PA, Schneeberger M, Matheis F, et al. Microbiota modulate sympathetic neurons via a gut-brain circuit. Nature. 2020;583(7816):441-446.
|
| [47] |
Spencer NJ, Hu H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat Rev Gastroenterol Hepatol. 2020;17(6):338-351.
|
| [48] |
Purkayastha S, Stokes M, Bell KR. Autonomic nervous system dysfunction in mild traumatic brain injury: a review of related pathophysiology and symptoms. Brain Inj. 2019;33(9):1129-1136.
|
| [49] |
Baguley IJ, Slewa-Younan S, Heriseanu RE, Nott MT, Mudaliar Y, Nayyar V. The incidence of dysautonomia and its relationship with autonomic arousal following traumatic brain injury. Brain Inj. 2007;21(11):1175-1181.
|
| [50] |
Bansal V, Costantini T, Kroll L, et al. Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis. J Neurotrauma. 2009;26(8):1353-1359.
|
| [51] |
Tang Y, Dong X, Chen G, et al. Vagus nerve stimulation attenuates early traumatic brain injury by regulating the NF-κB/NLRP3 signaling pathway. Neurorehabil Neural Repair. 2020;34(9):831-843.
|
| [52] |
Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci. 2018;12:49.
|
| [53] |
Bonaz B, Sinniger V, Pellissier S. Vagal tone: effects on sensitivity, motility, and inflammation. Neurogastroenterol Motil. 2016;28(4):455-462.
|
| [54] |
Rao M, Gershon MD. The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol. 2016;13(9):517-528.
|
| [55] |
Pavlov VA, Tracey KJ. Neural circuitry and immunity. Immunol Res. 2015;63(1-3):38-57.
|
| [56] |
Zhu C, Grandhi R, Patterson T, Nicholson S. A review of traumatic brain injury and the gut microbiome: insights into novel mechanisms of secondary brain injury and promising targets for neuroprotection. Brain Sci. 2018;8(6):113.
|
| [57] |
Callaway CCM, Kosofsky BE. Autonomic dysfunction following mild traumatic brain injury. Curr Opin Neurol. 2019;32(6):802-807.
|
| [58] |
Farzi A, Fröhlich EE, Holzer P. Gut microbiota and the neuroendocrine system. Neurotherapeutics. 2018;15(1):5-22.
|
| [59] |
Rea K, Dinan TG, Cryan JF. The brain-gut axis contributes to neuroprogression in stress-related disorders. mod trends. Pharmacopsychiatry. 2017;31:152-161.
|
| [60] |
Sudo N. Microbiome, HPA axis and production of endocrine hormones in the gut. Adv Exp Med Biol. 2014;817:177-194.
|
| [61] |
Russo R, Cristiano C, Avagliano C, et al. Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr Med Chem. 2018;25(32):3930-3952.
|
| [62] |
Bolte AC, Lukens JR. Neuroimmune cleanup crews in brain injury. Trends Immunol. 2021;42(6):480-494.
|
| [63] |
Hoffman AN, Taylor AN. Stress reactivity after traumatic brain injury: implications for comorbid post-traumatic stress disorder. Behav Pharmacol. 2019;30(2 and 3):115-121.
|
| [64] |
Dicks LMT. Gut bacteria and neurotransmitters. Microorganisms. 2022;10(9):1838.
|
| [65] |
Karakan T, Ozkul C, Küpeli Akkol E, Bilici S, Sobarzo-Sánchez E, Capasso R. Gut-brain-microbiota axis: antibiotics and functional gastrointestinal disorders. Nutrients. 2021;13(2):389.
|
| [66] |
Angoa-Pérez M, Zagorac B, Anneken JH, et al. Repetitive, mild traumatic brain injury results in a progressive white matter pathology, cognitive deterioration, and a transient gut microbiota dysbiosis. Sci Rep. 2020;10(1):8949.
|
| [67] |
Parker A, Fonseca S, Carding SR. Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut Microbes. 2020;11(2):135-157.
|
| [68] |
Panther EJ, Dodd W, Clark A, Lucke-Wold B. Gastrointestinal microbiome and neurologic injury. Biomedicines. 2022;10(2):500.
|
| [69] |
Liu X, Cao S, Zhang X. Modulation of gut microbiota-brain axis by probiotics, prebiotics, and diet. J Agric Food Chem. 2015;63(36):7885-7895.
|
| [70] |
Chudzik A, Orzyłowska A, Rola R, Stanisz GJ. Probiotics, prebiotics and postbiotics on mitigation of depression symptoms: modulation of the brain-gut-microbiome axis. Biomolecules. 2021;11(7):1000.
|
| [71] |
Rice MW, Pandya JD, Shear DA. Gut microbiota as a therapeutic target to ameliorate the biochemical, neuroanatomical, and behavioral effects of traumatic brain injuries. Front Neurol. 2019;10:875.
|
| [72] |
Wang H, He S, Xin J, et al. Psychoactive effects of Lactobacillus johnsonii against restraint stress-induced memory dysfunction in mice through modulating intestinal inflammation and permeability—a study based on the gut-brain axis hypothesis. Front Pharmacol. 2021;12:662148.
|
| [73] |
Suganya K, Koo BS. Gut-brain axis: role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions. Int J Mol Sci. 2020;21(20):7551.
|
| [74] |
Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021;12:578386.
|
| [75] |
Pérez-Carbonell L, Faulkner H, Higgins S, Koutroumanidis M, Leschziner G. Vagus nerve stimulation for drug-resistant epilepsy. Pract Neurol. 2020;20(3):189-198.
|
| [76] |
Austelle CW, O’Leary GH, Thompson S, et al. A comprehensive review of vagus nerve stimulation for depression. Neuromodulation. 2022;25(3):309-315.
|
| [77] |
Rodney T, Osier N, Gill J. Pro-and anti-inflammatory biomarkers and traumatic brain injury outcomes: a review. Cytokine. 2018;110:248-256.
|
| [78] |
Zhang H, Li C, Qu Y, Yang Y, Du J, Zhao Y. Effects and neuroprotective mechanisms of vagus nerve stimulation on cognitive impairment with traumatic brain injury in animal studies: a systematic review and meta-analysis. Front Neurol. 2022;13:963334.
|
| [79] |
Mader S, Brimberg L. Aquaporin-4 water channel in the brain and its implication for health and disease. Cells. 2019;8(2):90.
|
| [80] |
Dadgostar E, Rahimi S, Nikmanzar S, et al. Aquaporin 4 in traumatic brain injury: from molecular pathways to therapeutic target. Neurochem Res. 2022;47(4):860-871.
|
| [81] |
Clough RW, Neese SL, Sherill LK, et al. Cortical edema in moderate fluid percussion brain injury is attenuated by vagus nerve stimulation. Neuroscience. 2007;147(2):286-293.
|
| [82] |
Lopez NE, Krzyzaniak MJ, Costantini TW, et al. Vagal nerve stimulation decreases blood-brain barrier disruption after traumatic brain injury. J Trauma Acute Care Surg. 2012;72(6):1562-1566.
|
| [83] |
Davies DC. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. J Anat. 2002;200(6):639-646.
|
| [84] |
Kikuchi K, Tancharoen S, Matsuda F, et al. Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4. Biochem Biophys Res Commun. 2009;390(4):1121-1125.
|
| [85] |
Kigerl KA, Hall JCE, Wang L, Mo X, Yu Z, Popovich PG. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med. 2016;213(12):2603-2620.
|
| [86] |
Benakis C, Brea D, Caballero S, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells. Nature Med. 2016;22(5):516-523.
|
| [87] |
Grenham S, Clarke G, Cryan JF, Dinan TG. Brain-gut-microbe communication in health and disease. Front Physiol. 2011;2:94.
|
| [88] |
Wang JW, Kuo CH, Kuo FC, et al. Fecal microbiota transplantation: review and update. J Formos Med Assoc. 2019;118(suppl 1):S23-S31.
|
| [89] |
Antushevich H. Fecal microbiota transplantation in disease therapy. Clin Chim Acta. 2020;503:90-98.
|
| [90] |
Vendrik KEW, Ooijevaar RE, de Jong PRC, et al. Fecal microbiota transplantation in neurological disorders. Front Cell Infect Microbiol. 2020;10:98.
|
| [91] |
Singh V, Roth S, Llovera G, et al. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci. 2016;36(28):7428-7440.
|
| [92] |
Selvanantham T, Lin Q, Guo CX, et al. NKT cell-deficient mice harbor an altered microbiota that fuels intestinal inflammation during chemically induced colitis. J Immunol. 2016;197(11):4464-4472.
|
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