Background Bioactive lipids produced by human cells or by the gut microbiota might play an important role in health and disease. Dietary intakes are key determinants of the gut microbiota, its production of short-chain (SCFAs) and branched-chain fatty acids (BCFAs), and of the host endocannabinoidome signalling, which are all involved in metabolic diseases. This hypothesis-driven longitudinal fixed sequence nutritional study, realized in healthy participants, was designed to determine if a lead-in diet affects the host response to a short-term dietary intervention. Participants received a Mediterranean diet (MedDiet) for 3 days, a 13-day lead-in controlled diet reflecting the average Canadian dietary intake (CanDiet), and once again a MedDiet for 3 consecutive days. Fecal and blood samples were collected at the end of each dietary phase to evaluate alterations in gut microbiota composition and plasma levels of endocannabinoidome mediators, SCFAs, and BCFAs. Results We observed an immediate and reversible modulation of plasma endocannabinoidome mediators, BCFAs, and some SCFAs in response to both diets. BCFAs were more strongly reduced by the MedDiet when the latter was preceded by the lead-in CanDiet. The gut microbiota response was also immediate, but not all changes due to the CanDiet were reversible following a short dietary MedDiet intervention. Higher initial microbiome diversity was associated with reduced microbiota modulation after short-term dietary interventions. We also observed that BCFAs and 2-monoacylglycerols had many, but distinct, correlations with gut microbiota composition. Several taxa modulated by dietary intervention were previously associated to metabolic disorders, warranting the need to control for recent diet in observational association studies. Conclusions Our results indicate that lipid mediators involved in the communication between the gut microbiota and host metabolism exhibit a rapid response to dietary changes, which is also the case for some, but not all, microbiome taxa. The lead-in diet influenced the gut microbiome and BCFA, but not the endocannabinoidome, response to the MedDiet. A higher initial microbiome diversity favored the stability of the gut microbiota in response to dietary changes. This study highlights the importance of considering the previous diet in studies relating the gut microbiome with lipid signals involved in host metabolism.

The extended endocannabinoid system, also termed endocannabinoidome, participates in multiple metabolic functions in health and disease. Physical activity can both have an acute and chronic impact on endocannabinoid mediators, as does diet. In this crossover randomized controlled study, we investigated the influence of diet on the peripheral response to acute maximal aerobic exercise in a sample of active adult women (n = 7) with no underlying metabolic conditions. We compared the impact of 7-day standardized Mediterranean diet (MedDiet) and control diet inspired by Canadian macronutrient intake (CanDiet) on endocannabinoidome and short-chain fatty acid metabolites post maximal aerobic exercise. Overall, plasmatic endocannabinoids, their congeners and some polyunsaturated fatty acids increased significantly post maximal aerobic exercise upon cessation of exercise and recovered their initial values within 1 h after exercise. Most N-acylethanolamines and polyunsaturated fatty acids increased directly after exercise when the participants had consumed the MedDiet, but not when they had consumed the CanDiet. This impact was different for monoacylglycerol endocannabinoid congeners, which in most cases reacted similarly to acute exercise while on the MedDiet or the CanDiet. Fecal microbiota was only minimally affected by the diet in this cohort. This study demonstrates that endocannabinoidome mediators respond to acute maximal aerobic exercise in a way that is dependent on the diet consumed in the week prior to exercise.

Dietary micronutrients act at the intestinal level, thereby influencing microbial communities, the host endocannabinoidome, and immune and anti-oxidative response. Selenium (Se) is a trace element with several health benefits. Indeed, Se plays an important role in the regulation of enzymes with antioxidative and anti-inflammatory activity as well as indicators of the level of oxidative stress, which, together with chronic low-grade inflammation, is associated to obesity. To understand how Se variations affect diet-related metabolic health, we fed female and male mice for 28 days with Se-depleted or Se-enriched diets combined with low- and high-fat/sucrose diets. We quantified the plasma and intestinal endocannabinoidome, profiled the gut microbiota, and measured intestinal gene expression related to the immune and the antioxidant responses in the intestinal microenvironment. Overall, we show that intestinal segment-specific microbiota alterations occur following high-fat or low-fat diets enriched or depleted in Se, concomitantly with modifications of circulating endocannabinoidome mediators and changes in cytokine and antioxidant enzyme expression. Specifically, Se enrichment was associated with increased circulating plasma levels of 2-docosahexaenoyl-glycerol (2-DHG), a mediator with putative beneficial actions on metabolism and inflammation. Others eCBome mediators also responded to the diets. Concomitantly, changes in gut microbiota were observed in Se-enriched diets following a high-fat diet, including an increase in the relative abundance of Peptostreptococcaceae and Lactobacillaceae. With respect to the intestinal immune response and anti-oxidative gene expression, we observed a decrease in the expression of proinflammatory genes Il1β and Tnfα in high-fat Se-enriched diets in caecum, while in ileum an increase in the expression levels of the antioxidant gene Gpx4 was observed following Se depletion. The sex of the animal influenced the response to the diet of both the gut microbiota and endocannabinoid mediators. These results identify Se as a regulator of the gut microbiome and endocannabinoidome in conjunction with high-fat diet, and might be relevant to the development of new nutritional strategies to improve metabolic health and chronic low-grade inflammation associated to metabolic disorders.