LAUSR

BACKGROUND & AIMS 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. METHODS 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: 1 g/ml, Vancomycin: 0.5 g/ml, Imipenem: 0.25 g/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. RESULTS 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. CONCLUSIONS 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.