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DOI: 10.1055/s-0046-1815929
Neurotrauma and the Gut–Brain Axis: Mechanistic Insights and Therapeutic Implications
Autor*innen
Abstract
The gut–brain axis (GBA) represents a complex bidirectional communication network linking the gastrointestinal tract and the central nervous system through neural, immune, endocrine, and metabolic pathways. Increasing evidence indicates that traumatic brain injury (TBI) and spinal cord injury (SCI) disrupt gut microbial homeostasis, resulting in dysbiosis, increased intestinal permeability, systemic inflammation, and secondary neurological injury. Alterations in microbial composition, depletion of short-chain fatty acid–producing bacteria, and dysregulated immune signaling contribute to neuroinflammation and multisystem dysfunction following neurotrauma. Experimental studies highlight the role of microbial metabolites, inflammatory mediators, enteroendocrine signaling, and vagal pathways in modulating neurological outcomes. Emerging therapeutic strategies targeting the GBA, including probiotics, prebiotics, dietary modification, short-chain fatty acid supplementation, fecal microbiota transplantation, amino acid supplementation, and judicious antibiotic use have shown promise in attenuating inflammation and supporting recovery. However, robust clinical evidence remains limited. This narrative review synthesizes current knowledge on the pathophysiological mechanisms linking the gut and brain in neurotrauma, evaluates existing and emerging therapeutic interventions, and identifies key gaps in knowledge that must be addressed to translate microbiome-based strategies into effective clinical therapies.
Keywords
gut–brain axis - neurotrauma - gut microbiota - dysbiosis - neuro-immuno-endocrine pathwaysPublikationsverlauf
Artikel online veröffentlicht:
28. Januar 2026
© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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References
- 1 Lewandowska-Pietruszka Z, Figlerowicz M, Mazur-Melewska K. The history of the intestinal microbiota and the gut-brain axis. Pathogens 2022; 11 (12) 1540
- 2 Loh JS, Mak WQ, Tan LKS. et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther 2024; 9 (01) 37
- 3 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
- 4 Ghaemi M, Kheradmand D. The gut-brain axis in traumatic brain Injury: literature review. J Clin Neurosci 2025; 136: 111258
- 5 Bao W, Sun Y, Lin Y, Yang X, Chen Z. An integrated analysis of gut microbiota and the brain transcriptome reveals host-gut microbiota interactions following traumatic brain injury. Brain Res 2023; 1799: 148149
- 6 Houlden A, Goldrick M, Brough D. et al. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production. Brain Behav Immun 2016; 57: 10-20
- 7 Munley JA, Kelly LS, Park G. et al. Multicompartmental traumatic injury induces sex-specific alterations in the gut microbiome. J Trauma Acute Care Surg 2023; 95 (01) 30-38
- 8 Sgro M, Iacono G, Yamakawa GR, Kodila ZN, Marsland BJ, Mychasiuk R. Age matters: microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats. PLoS One 2022; 17 (11) e0278259
- 9 Rusch JA, Layden BT, Dugas LR. Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis. Front Endocrinol (Lausanne) 2023; 14: 1130689
- 10 Faraji N, Payami B, Ebadpour N, Gorji A. Vagus nerve stimulation and gut microbiota interactions: a novel therapeutic avenue for neuropsychiatric disorders. Neurosci Biobehav Rev 2025; 169: 105990
- 11 El Baassiri MG, Raouf Z, Badin S, Escobosa A, Sodhi CP, Nasr IW. Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies. J Neuroinflammation 2024; 21 (01) 124
- 12 Cannon AR, Anderson LJ, Galicia K. et al. Traumatic brain injury–induced inflammation and gastrointestinal motility dysfunction. Shock 2023; 59 (04) 621-626
- 13 Ritter K, Vetter D, Wernersbach I, Schwanz T, Hummel R, Schäfer MKE. Pre-traumatic antibiotic-induced microbial depletion reduces neuroinflammation in acute murine traumatic brain injury. Neuropharmacology 2023; 237: 109648
- 14 Shen H, Xu B, Yang C. et al. A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury. Biomaterials 2022; 280: 121279
- 15 Zhang N, Yin Y, Xu SJ, Wu YP, Chen WS. Inflammation & apoptosis in spinal cord injury. Indian J Med Res 2012; 135 (03) 287-296
- 16 Postolache TT, Wadhawan A, Can A. et al. Inflammation in traumatic brain injury. J Alzheimers Dis 2020; 74 (01) 1-28
- 17 Weaver JL. The brain-gut axis: a prime therapeutic target in traumatic brain injury. Brain Res 2021; 1753: 147225
- 18 Waters RJ, Murray GD, Teasdale GM. et al. Cytokine gene polymorphisms and outcome after traumatic brain injury. J Neurotrauma 2013; 30 (20) 1710-1716
- 19 Diamond ML, Ritter AC, Failla MD. et al. IL-1β associations with posttraumatic epilepsy development: a genetics and biomarker cohort study. Epilepsia 2015; 56 (07) 991-1001
- 20 Hou P, Yang Y, Li Z. et al. TAK-3 inhibits lipopolysaccharide-induced neuroinflammation in traumatic brain injury rats through the TLR-4/NF-κB pathway. J Inflamm Res 2024; 17: 2147-2158
- 21 Carecho R, Carregosa D, Ratilal BO. et al. Dietary (poly)phenols in traumatic brain injury. Int J Mol Sci 2023; 24 (10) 8908
- 22 Theadom A, Mahon S, Barker-Collo S. et al. Enzogenol for cognitive functioning in traumatic brain injury: a pilot placebo-controlled RCT. Eur J Neurol 2013; 20 (08) 1135-1144
- 23 Shao X, Hu Q, Chen S, Wang Q, Xu P, Jiang X. Ghrelin ameliorates traumatic brain injury by down-regulating bFGF and FGF-BP. Front Neurosci 2018; 12: 445
- 24 Goksu AY, Kocanci FG, Akinci E. et al. Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration. Eur J Neurosci 2024; 59 (08) 1993-2015
- 25 Li D, Yu S, Long Y. et al. Tryptophan metabolism: mechanism-oriented therapy for neurological and psychiatric disorders. Front Immunol 2022; 13: 985378
- 26 Ma Y, Liu T, Fu J. et al. Lactobacillus acidophilus exerts neuroprotective effects in mice with traumatic brain injury. J Nutr 2019; 149 (09) 1543-1552
- 27 Pagkou D, Kogias E, Foroglou N, Kotzampassi K. Probiotics in traumatic brain injury: new insights into mechanisms and future perspectives. J Clin Med 2024; 13 (15) 4546
- 28 Cotoia A, Charitos IA, Corriero A, Tamburrano S, Cinnella G. The role of macronutrients and gut microbiota in neuroinflammation post-traumatic brain injury: a narrative review. Nutrients 2024; 16 (24) 4359
- 29 Holcomb M, Marshall AG, Flinn H. et al. Probiotic treatment induces sex-dependent neuroprotection and gut microbiome shifts after traumatic brain injury. J Neuroinflammation 2025; 22 (01) 114
- 30 Kigerl KA, Mostacada K, Popovich PG. Gut microbiota are disease-modifying factors after traumatic spinal cord injury. Neurotherapeutics 2018; 15 (01) 60-67
- 31 Raposo PJF, Nguyen AT, Schmidt EKA. et al. No beneficial effects of the Alfasigma VSL#3 probiotic treatment after cervical spinal cord injury in rats. Top Spinal Cord Inj Rehabil 2025; 31 (01) 1-16
- 32 Li C, Lu F, Chen J, Ma J, Xu N. Probiotic supplementation prevents the development of ventilator-associated pneumonia for mechanically ventilated ICU patients: a systematic review and network meta-analysis of randomized controlled trials. Front Nutr 2022; 9: 919156
- 33 Dong J, Xie T, Shi C. et al. Gut-spinal cord axis in spinal cord injury: bidirectional inflammatory mechanisms and microbiota-targeted therapeutic strategies. J Inflamm Res 2025; 18: 12549-12573
- 34 Cui Y, Liu J, Lei X. et al. Dual-directional regulation of spinal cord injury and the gut microbiota. Neural Regen Res 2024; 19 (03) 548-556
- 35 Opeyemi OM, Rogers MB, Firek BA. et al. Sustained dysbiosis and decreased fecal short-chain fatty acids after traumatic brain injury and impact on neurologic outcome. J Neurotrauma 2021; 38 (18) 2610-2621
- 36 Davis Iv BT, Han H, Islam MBAR. et al. Short chain fatty acid supplementation after traumatic brain injury attenuates neurologic injury via the gut-brain-microglia axis. Shock 2025; . Epub ahead of print
- 37 Wu A, Ying Z, Gomez-Pinilla F. Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 2004; 21 (10) 1457-1467
- 38 Patel PR, Armistead-Jehle P, Eltman NR, Heath KM, Cifu DX, Swanson RL. Brain injury: how dietary patterns impact long-term outcomes. Curr Phys Med Rehabil Rep 2023; 11 (03) 367-376
- 39 Bakkar NMZ, Ibeh S, AlZaim I, El-Yazbi AF, Kobeissy F. High-fat diets in traumatic brain injury: a ketogenic diet resolves what the Western diet messes up neuroinflammation and beyond. In: CR, Patel VB, Preedy VR. eds. Diet and Nutrition in Neurological Disorders. Elsevier: Amsterdam: Academic Press; 2023: 175-197
- 40 Hu X, Jin H, Yuan S. et al. Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis. Front Cell Infect Microbiol 2023; 13: 1254610
- 41 Simon DW, Rogers MB, Gao Y. et al. Depletion of gut microbiota is associated with improved neurologic outcome following traumatic brain injury. Brain Res 2020; 1747: 147056

