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Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)

  • Authors:
    • Xigang Ma
    • Yongsen Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu 730900, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 188
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    Published online on: May 14, 2026
       https://doi.org/10.3892/ijmm.2026.5859
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Abstract

The gut‑brain axis (GBA) has emerged as a critical mediator of acute brain dysfunction, particularly postoperative delirium and sepsis‑associated encephalopathy, in surgical and critically ill patients. Anesthesia, surgical stress, and critical illness collectively disrupt gut microbiota composition and intestinal barrier integrity, leading to increased systemic translocation of microbial products. This process triggers neuroinflammation and compromises blood‑brain barrier function through defined molecular pathways, including alterations in microbe‑derived short‑chain fatty acids, tryptophan metabolites, and potent neuroimmune signaling via the LPS‑TLR4‑NF‑κB axis. The present review synthesizes current evidence on the molecular crosstalk within the GBA, highlighting how perioperative and intensive care interventions drive dysbiosis and subsequent neurological sequelae. Furthermore, it evaluates promising GBA‑targeted therapeutic strategies, including dietary modulation, biotherapeutics and pharmacological interventions, are evaluated for their potential to mitigate delirium and improve long‑term cognitive outcomes. A deeper understanding of these mechanisms is essential for developing novel preventive and therapeutic approaches in vulnerable patient populations.
View Figures

Figure 1

Gut-brain architecture under
anesthesia and stress (https://www.figdraw.com/static/index.html#/; 2.0
version). LPS, lipopolysaccharide; BBB, blood-brain barrier; GALT,
gut-associated lymphoid tissue.

Figure 2

Microbial metabolite signaling and
delirium pathogenesis (https://www.figdraw.com/static/index.html#/; 2.0
version). BBB, blood-brain barrier; CYP3A4, cytochrome P450 3A4;
FFAR3, free fatty acid receptor 3; HDAC, histone deacetylase;
IDO-1, indoleamine 2,3-dioxygenase 1; LPS, lipopolysaccharide;
NLRP3, NOD-like receptor protein 3; NMDA, N-methyl-D-aspartate;
SCFA, short-chain fatty acid; TLR4, Toll-like receptor 4.
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Copy and paste a formatted citation
Spandidos Publications style
Ma X and Zhao Y: Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review). Int J Mol Med 58: 188, 2026.
APA
Ma, X., & Zhao, Y. (2026). Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review). International Journal of Molecular Medicine, 58, 188. https://doi.org/10.3892/ijmm.2026.5859
MLA
Ma, X., Zhao, Y."Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)". International Journal of Molecular Medicine 58.1 (2026): 188.
Chicago
Ma, X., Zhao, Y."Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)". International Journal of Molecular Medicine 58, no. 1 (2026): 188. https://doi.org/10.3892/ijmm.2026.5859
Copy and paste a formatted citation
x
Spandidos Publications style
Ma X and Zhao Y: Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review). Int J Mol Med 58: 188, 2026.
APA
Ma, X., & Zhao, Y. (2026). Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review). International Journal of Molecular Medicine, 58, 188. https://doi.org/10.3892/ijmm.2026.5859
MLA
Ma, X., Zhao, Y."Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)". International Journal of Molecular Medicine 58.1 (2026): 188.
Chicago
Ma, X., Zhao, Y."Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)". International Journal of Molecular Medicine 58, no. 1 (2026): 188. https://doi.org/10.3892/ijmm.2026.5859
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