Analysis of lipid metabolites derived from gut microbiota in ischemia-reperfusion model

Abstract

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.