Altered endocannabinoidome bioactive lipid levels accompany reduced DNBS-induced colonic inflammation in germ-free mice

Lipids in Health and Disease

Research

Nicolas Flamand¹  Nadine Leblanc¹  Cristoforo Silvestri²  Francesca Borrelli³  Tommaso Venneri³  Giada Giorgini⁴  Vincenzo Di Marzo⁵ 

[1] Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de Médecine, Université Laval, Québec, Canada;Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de Médecine, Université Laval, Québec, Canada;Centre NUTRISS, École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Institut sur la Nutrition et les Aliments Fonctionnels, Université Laval, Québec, Canada;Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy;Joint International Research Unit (JIRU) for Chemical and Biomolecular Research on the Microbiome and its impact on Metabolic Health and Nutrition (MicroMeNu) between Université Laval and the Consiglio Nazionale delle Ricerche (CNR), Institute of Biomolecular Chemistry, Pozzuoli, NA, Italy;Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de Médecine, Université Laval, Québec, Canada;Joint International Research Unit (JIRU) for Chemical and Biomolecular Research on the Microbiome and its impact on Metabolic Health and Nutrition (MicroMeNu) between Université Laval and the Consiglio Nazionale delle Ricerche (CNR), Institute of Biomolecular Chemistry, Pozzuoli, NA, Italy;Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Département de médecine, Faculté de Médecine, Université Laval, Québec, Canada;Centre NUTRISS, École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation (FSAA), Institut sur la Nutrition et les Aliments Fonctionnels, Université Laval, Québec, Canada;Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Québec, Canada;

关键词: 2,4-dinitrobenzenesulfonic acid (DNBS);    Colitis;    Endocannabinoids;    Microbiome;    Antibiotics;    Germ-free mice;    Inflammation;   

DOI  :  10.1186/s12944-023-01823-1

 received in 2023-01-26, accepted in 2023-04-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGut microbiota are involved in the onset and development of chronic intestinal inflammation. The recently described endocannabinoidome (eCBome), a diverse and complex system of bioactive lipid mediators, has been reported to play a role in various physio-pathological processes such as inflammation, immune responses and energy metabolism. The eCBome and the gut microbiome (miBIome) are closely linked and form the eCBome - miBIome axis, which may be of special relevance to colitis.MethodsColitis was induced in conventionally raised (CR), antibiotic-treated (ABX) and germ-free (GF) mice with dinitrobenzene sulfonic acid (DNBS). Inflammation was assessed by Disease Activity Index (DAI) score, body weight change, colon weight-length ratio, myeloperoxidase (MPO) activity and cytokine gene expression. Colonic eCBome lipid mediator concentrations were measured by HPLC-MS /MS.ResultsGF mice showed increased levels of anti-inflammatory eCBome lipids (LEA, OEA, DHEA and 13- HODE-EA) in the healthy state and higher MPO activity. DNBS elicited reduced inflammation in GF mice, having lower colon weight/length ratios and lower expression levels of Il1b, Il6, Tnfa and neutrophil markers compared to one or both of the other DNBS-treated groups. Il10 expression was also lower and the levels of several N-acyl ethanolamines and 13-HODE-EA levels were higher in DNBS-treated GF mice than in CR and ABX mice. The levels of these eCBome lipids negatively correlated with measures of colitis and inflammation.ConclusionsThese results suggest that the depletion of the gut microbiota and subsequent differential development of the gut immune system in GF mice is followed by a compensatory effect on eCBome lipid mediators, which may explain, in part, the observed lower susceptibility of GF mice to develop DNBS-induced colitis.

【 授权许可】

CC BY   
© The Author(s) 2023

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