Lactobacillus amplifies DHAMaR1 conversion to attenuate intestinal ischemia-reperfusion injury via decreasing...

Area of Science:

• Gastroenterology
• Inflammation research
• Microbiome research

Background:

• Maresin1 (MaR1), a docosahexaenoic acid (DHA)-derived mediator, has anti-inflammatory and cytoprotective properties.
• The precise role and mechanisms of MaR1 in intestinal ischemia-reperfusion (I/R) injury require further elucidation.

Purpose of the Study:

• To investigate the therapeutic potential and underlying mechanisms of MaR1 in a murine model of intestinal I/R injury.
• To explore the impact of DHA and Lactobacillus supplementation, individually and in combination, on intestinal I/R injury.

Main Methods:

• Established a murine model of intestinal I/R injury.
• Utilized knockout mice for Retinoic acid receptor-related orphan receptor alpha (RORα) and gasdermin D (GSDMD) to study signaling pathways.
• Administered MaR1 or supplemented with DHA and/or Lactobacillus, assessing intestinal injury, inflammation, and pyroptosis.
• Employed multi-omics approaches (16S rRNA sequencing, transcriptomics, metabolomics) to analyze host-microbe interactions.

Main Results:

• MaR1 administration significantly reduced epithelial injury and pyroptosis, dependent on RORα and GSDMD.
• Dietary DHA supplementation increased systemic MaR1 levels and conferred protection against I/R injury.
• Combined DHA and Lactobacillus supplementation demonstrated synergistic protective effects, with Lactobacillus enhancing DHA-to-MaR1 conversion.
• Multi-omics analyses revealed coordinated regulation of inflammatory pathways and microbial metabolic activity.

Conclusions:

• MaR1 and DHA provide significant protection against intestinal I/R injury by suppressing RORα-mediated pyroptosis.
• Probiotic-enhanced MaR1 biosynthesis represents a novel crosstalk between microbiota and lipid mediators with therapeutic implications.
• Combination therapies targeting host-microbe interactions offer a promising strategy for managing ischemic intestinal injury.