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

Abstract

BACKGROUND:

Gut 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.

METHODS:

Colitis 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.

RESULTS:

GF 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.

CONCLUSIONS:

These 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.

• Authors: Tommaso Venneri, Giada Giorgini, Nadine Leblanc, Nicolas Flamand, Francesca Borrelli, Cristoforo Silvestri, Vincenzo Di Marzo
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 22 Issue 1 Pg. 63 (May 15 2023) ISSN: 1476-511X [Electronic] England
• PMID: 37189092 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Dinitrobenzenes
• 2,4-dinitrofluorobenzene sulfonic acid
• Lipids

Topics

• Mice
• Animals
• Dinitrobenzenes (adverse effects)
• Colitis (chemically induced, genetics, metabolism)
• Inflammation
• Lipids