Abstract
Oxylipins (OXLs) are bioactive lipid metabolites derived from polyunsaturated fatty acids (PUFAs) which act as signaling molecules and are involved in inflammatory processes such as those that occur in obesity. On the other hand, gut microbiota plays an essential role in regulating inflammatory responses. However, little is known about the potential impact of gut bacteria on OXLs metabolism. Thus, the objective of this study was to investigate the effect of gut microbiota dysbiosis on plasma oxylipins profile in healthy and diet-induced obese animals. Eight-week-old male Wistar rats were fed with either a standard or cafeteria diet (CAF) for 5 weeks and administered an antibiotic cocktail (ABX) in the drinking water (Ampicillin: 1g/ml, Vancomycin: 0.5g/ml, Imipenem: 0.25g/ml) for the last 2 weeks in order to induce gut microbiota dysbiosis. Metabolomics analysis of OXLs in plasma was performed by HPLC-MS analysis. No antibiotic treated animals were included as controls. Plasma OXLs profile was significantly altered due to both CAF feeding and ABX administration. ABX effect was more pronounced under obesogenic conditions. Several significant correlations between different bacteria taxa and these lipid mediators were observed. Among these, the positive correlation of Proteobacteria with LTB4, a proinflammatory OXL involved in obesity-related disorders, was especially remarkable. Gut microbiota plays a key role in regulating these lipid metabolites and, therefore, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. Moreover, this can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles.
Highlights
Oxylipins (OXLs) are bioactive lipid mediators, mainly generated by the oxidation of polyunsaturated fatty acids (PUFAs) by lipoxygenases (LOXs), which can lead to the activation of inflammatory response as well as to the resolution and prevention of acute [1] and chronic inflammatoryJ
For the first time to our knowledge, that gut microbiota dysbiosis significantly alter plasmatic OXLs levels in healthy and obesity conditions induced by cafeteria diet (CAF), suggesting a key role for gut bacteria in the metabolism of these inflammatory lipid mediators
These findings collectively confirmed that the administration of this high-fat high-sugar diet for 5 weeks was enough to induce both obesity and glucose intolerance, and that gut microbiota dysbiosis induced by ABX administration altered glucose tolerance response in these animals
Summary
Oxylipins (OXLs) are bioactive lipid mediators, mainly generated by the oxidation of PUFAs by lipoxygenases (LOXs), which can lead to the activation of inflammatory response as well as to the resolution and prevention of acute [1] and chronic inflammatoryJ. Activity) and the removal of immune cells from the inflamed site (pro-resolving activity) [7e9] In this pro-resolving environment, OXLs are subsequently transformed giving rise to a great variety of oxylipin metabolites such as lipoxins, resolvins, protectins and maresins. These lipid mediators have pivotal biological functions promoting the resolution of inflammatory processes and homeostasis [10]. Conclusions: Gut microbiota plays a key role in regulating these lipid metabolites and, affecting oxylipins-mediated inflammatory processes. These results are the first evidence to our knowledge of gut microbiota impact on OXLs metabolism. This can set the basis for developing new obesity markers based on OXLs and gut microbiota profiles
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