Beyond organ isolation: The bidirectional crosstalk between cerebral and intestinal ischemia-reperfusion injury via microbiota-gut-brain axis

Biochem Biophys Res Commun. 2025 May 12:763:151804. doi: 10.1016/j.bbrc.2025.151804. Epub 2025 Apr 11.

Abstract

Ischemia-reperfusion injury (IRI) represents a pathophysiological phenomenon of profound clinical relevance that poses considerable threats to patient safety. IRI may manifest in a variety of clinical contexts including, but not limited to, sepsis, organ transplantation, shock, myocardial infarction, cerebral ischemia, and stroke. Critically, IRI exhibits complex interactions across different organs, with effects that surpass mere localized tissue damage. These impacts can amplify damage to both adjacent and remote organs through pathways such as the gut-brain axis and the gut-lung axis, facilitated by intricate signaling mechanisms. Noteworthy is the interaction between gut IRI and brain IRI, which involves sophisticated neuroendocrine, systemic, and immune mechanisms coordinated through the microbiome-gut-brain axis. This review seeks to delve into the intricate interactions between gut and brain IRI, viewed through the lens of the microbiota-gut-brain axis. It aims to assess its translational potential in clinical settings, provide a theoretical foundation for developing relevant therapeutic strategies, and pinpoint novel directions for research.

Keywords: Gut; Ischemia-reperfusion injury; Metabolic products; Microbiota; Microbiota-gut-brain axis.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia* / microbiology
  • Brain Ischemia* / pathology
  • Brain* / metabolism
  • Brain* / pathology
  • Brain-Gut Axis*
  • Gastrointestinal Microbiome*
  • Humans
  • Intestines* / microbiology
  • Intestines* / pathology
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / microbiology
  • Reperfusion Injury* / pathology