Dietary iron interacts with diet composition to modulate the endocannabinoidome and the gut microbiome in mice

The intake of dietary iron (Fe) affects both the intestine and its many resident bacteria. Here, we evaluated how 28 days of Fe depletion and enrichment, in interaction with Low Fat-Low Sucrose (LFLS) or High Fat-High Sucrose (HFHS) diets, affect the host via the expanded endocannabinoid system, or endocannabinoidome, and modulate intestinal gut microbial communities. Circulating levels of N-oleoyl ethanolamine (OEA) showed an elevation associated with Fe-enriched LFLS diet, while the Fe-depleted HFHS diet showed an elevation of N-arachidonoyl-ethanolamine (AEA). In parallel, the response of intestinal inflammatory mediators to Fe in the diet showed decreased levels of prostaglandins PGE1, PGE3 and 1a,1b-dihomo PGF2a in the caecum, without significant changes in the expression of intestinal genes associated with inflammation. Individual differences in microbial taxa were less pronounced in the ileum than in the caecum, where Eubacterium coprostanoligenes group showed an increase in relative abundance associated with Fe-depleted LFLS diets. In conclusion, our study shows that the effect of Fe intake on the host is dependent on overall diet composition, with significant impact on some circulating N-acyl ethanolamine levels, caecal prostaglandin concentrations and microbiota composition.