Mechanistic investigation of the crosstalk between hepatic ischemia-reperfusion injury and intestinal microbiota.

Hepatic ischemia-reperfusion injury (HIRI) represents a significant and clinically critical pathological phenomenon encountered in liver transplantation, major hepatectomy, severe trauma, and shock resuscitation. It has a direct impact on postoperative liver function recovery, graft prognosis, and patient outcomes. The pathogenesis of HIRI is complex and multifactorial, encompassing oxidative stress, intracellular calcium overload, various modes of programmed cell death, aberrant immune activation, and microcirculatory dysfunction. The 'gut-liver axis' theory has recently highlighted the complex relationship between gut microbiota and HIRI. This review systematically elucidates the reciprocal interactions between HIRI and gut microbiota. On one hand, HIRI induces splanchnic hypoperfusion and systemic inflammatory responses, leading to reduced microbial diversity, altered commensal structure, disrupted metabolic profiles, and compromised intestinal barrier integrity through the disruption of tight junctions. On the other hand, dysbiotic gut microbiota and its bioactive metabolites, such as short-chain fatty acids and indole derivatives, can translocate to the liver via the compromised barrier and portal circulation. This translocation exacerbates hepatic inflammation, oxidative stress, and hepatocellular death by activating pattern recognition receptors, regulating immune cell function, and modulating energy metabolism. A comprehensive understanding of this interactive network is essential for elucidating the systemic pathogenesis of HIRI and offers novel translational insights for the development of gut microbiota-targeted prevention and treatment strategies.