Seal and fish oils partially counteract inflammation and modulate endocannabinoidome lipid and oxylipin alterations in DSS-induced colitis.

Colitis is associated with endocannabinoidome (eCBome) and gut microbiome alterations, both of which are influenced by the diet, and thus may be modulated through nutritional components as potential therapeutic targets for colitis. We assessed the effects of n-3 polyunsaturated fatty acid (PUFA)-rich fish (FO) and seal (SO) oils in the dextran sodium sulphate (DSS) colitis mouse model. Mice were assessed for effects on inflammation, intestinal permeability, anxiety-like behaviour, gut microbiota composition and colon, blood and brain eCBome mediator levels. While neither FO or SO counteracted DSS-induced loss of weight, SO mitigated the increase in intestinal permeability and was more efficacious at reducing inflammation markers (Il1b, Il6, Tnfa and Arg1) than FO. DSS-induced changes in the bacterial community were not altered by FO or SO, which however mitigated alterations in the abundance of the Family XII UCG01 genera. DSS altered several eCBome and oxylipin bioactive lipid levels in a tissue-specific manner. FO and/or SO counteracted some of these changes, especially by increasing the levels of those lipids derived from n-3 PUFAs, many of which have anti-inflammatory activities. Interestingly, the novel eicosapentaenoic acid-derived eCBome mediator 2-eicosapentaenoyl glycerol was a top defining lipid of both FO and SO groups in all tissues. These data point to FO and, particularly SO, as potentially beneficial treatments of colitis through alterations in the eCBome, which is dysregulated in colitis.