Mechanisms of Autophagy and Inflammatory Response Crosstalk in Sepsis-Associated Intestinal Dysfunction

Area of Science:

• Gastroenterology
• Immunology
• Critical Care Medicine

Background:

• Sepsis-associated intestinal dysfunction (SAID) is a critical factor in multiorgan failure.
• Dysregulated autophagy-inflammation crosstalk underlies SAID pathophysiology.
• Current therapies for SAID are limited.

Purpose of the Study:

• To review the pathophysiology of SAID.
• To evaluate autophagy-targeted interventions for SAID.
• To explore novel intestinal-specific therapeutic targets.

Main Methods:

• Systematic review of preclinical and clinical studies.
• Analysis of the role of autophagy in maintaining intestinal barrier integrity.
• Evaluation of emerging therapeutic targets.

Main Results:

• Autophagy impairment by inflammatory mediators creates a pathogenic cycle.
• Preclinical studies show benefits from rapamycin, TFEB agonists, ATG5 overexpression, and NLRP3 siRNA.
• Clinical efficacy seen with IL-1 receptor antagonists in specific sepsis subpopulations.

Conclusions:

• Targeting the autophagy-inflammation axis is a promising therapeutic strategy for SAID.
• Novel targets like aquaporin-3 (AQP3), ghrelin, and Nur77 show potential.
• Clinical translation requires human-relevant models and precision medicine for disease heterogeneity.