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Updated: Jul 8, 2025
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model
Keita Nakatsutsumi1, Koji Morishita, Todd W Costantini
1From the Trauma and Acute Critical Care Center (K.N., K.M. M.K., T.A., A.S., K.S.), Tokyo Medical and Dental University Hospital, Tokyo, Japan; Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery (K.N., T.W.C.), University of California, San Diego, California; Department of Acute Critical Care and Disaster Medicine (M.K.), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Emergency and Critical Care Center (M.K.), Tokyo Women's Medical University, Adachi Medical Center, Tokyo; Laboratory for Metabolomics (M.A.), RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa; Division of Physiological Chemistry and Metabolism (M.A.), Graduate School of Pharmaceutical Sciences, Keio University; and National Hospital Organization Disaster Medical Center (Y.O.), Tokyo, Japan.
Background:
Disruption of intestinal barrier caused by intestinal ischemia due to hemorrhagic shock is associated with the pathogenesis of multiple organ dysfunction (MOD) after severe trauma. Mesenteric lymph (ML) plays an important role as a route for transporting inflammatory mediators, including lipids. Postbiotics, such as 10-hydroxy-cis-12-octadecenoic acid (HYA), have received much attention as a treatment option. However, the relationship between postbiotics and MOD has yet to be clarified. The aim of the present study was to analyze lipid metabolites derived from gut microbiota in the intestinal ischemia-reperfusion (IR) rat model.
Methods:
Male Sprague-Dawley rats underwent laparotomy, and their ML duct and superior mesenteric artery were exposed. The superior mesenteric artery was clamped for 60 minutes, followed by 120 minutes of reperfusion. The ML and the plasma were collected before and after intestinal IR. Lipids were extracted from plasma and ML, and liquid chromatography-tandem mass spectrometry was performed.
Results:
The concentration of linoleic acid in plasma samples was not different before and after IR; however, the linoleic acid concentration in the ML samples increased after intestinal IR. Eicosapentaenoic acids and docosahexaenoic related to linoleic acids showed similar changes with IR-induced increase in the ML. The concentration of HYA, a linoleic acid-derived bioactive metabolite produced by gut bacteria, was high in ML samples, while that in plasma samples was low. The relative increase rate of HYA in ML samples after IR was higher than that of the plasma samples (the ML samples: relative increase, 3.23 ± 1.36; the plasma samples: relative increase, 0.95 ± 0.35; n = 3, p = 0.048).
Conclusion:
The present study demonstrated increased linoleic acids and high concentrations of HYA, lipid metabolites derived from gut bacteria in the ML after intestinal IR. These findings may contribute to clarifying the relation between gut microbiota and MOD after severe trauma.
Insights
Intestinal ischemia increases gut bacteria-derived lipids like linoleic acid and 10-hydroxy-cis-12-octadecenoic acid (HYA) in mesenteric lymph. This highlights a link between gut microbiota and multiple organ dysfunction (MOD) after trauma.
Area of Science:
- Gastroenterology
- Metabolomics
- Trauma Pathophysiology
Background:
- Intestinal barrier disruption from ischemia-reperfusion (IR) injury contributes to multiple organ dysfunction (MOD) after severe trauma.
- Mesenteric lymph (ML) is a key route for inflammatory mediator transport, including lipids.
- Postbiotics, such as 10-hydroxy-cis-12-octadecenoic acid (HYA), are potential treatments, but their role in MOD is unclear.
Purpose of the Study:
- To investigate lipid metabolites derived from gut microbiota in an intestinal IR rat model.
- To analyze changes in lipid profiles within mesenteric lymph and plasma following IR injury.
Main Methods:
- Male Sprague-Dawley rats underwent a 60-minute superior mesenteric artery (SMA) occlusion followed by 120 minutes of reperfusion.
- Mesenteric lymph (ML) and plasma were collected pre- and post-IR.
- Lipid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed for analysis.
Main Results:
- Linoleic acid concentrations increased in ML but not plasma after IR.
- Gut microbiota-derived 10-hydroxy-cis-12-octadecenoic acid (HYA) showed higher concentrations in ML compared to plasma.
- The relative increase of HYA in ML post-IR was significantly higher than in plasma (3.23 vs. 0.95, p=0.048).
Conclusions:
- Intestinal IR leads to increased linoleic acids and HYA in ML, originating from gut bacteria.
- These findings suggest a connection between gut microbiota-derived lipid metabolites and MOD development post-trauma.
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