The human milk endocannabinoidome and neonatal growth in gestational diabetes.

Objective: Endocannabinoids and their N-acyl-ethanolamines (NAEs) and 2monoacyl-glycerols (2-MAGs) congeners are involved in the central and peripheral regulation of energy homeostasis, they are present in human milk and are associated with obesity. Infants exposed in utero to gestational diabetes mellitus (GDM) are more likely to develop obesity. The objective of this cross-sectional study is to compare the profile of eCBome mediators in milk of women with gestational diabetes (GDM+) and without (GDM-) and to assess the association with offspring growth. The hypothesis is that the eCBome of GDM+ human milk is altered and associated with a difference in infant growth. Methods: Circulating eCBome mediators were measured by LC-MS/MS in human milk obtained at 2 months postpartum from GDM+ (n=24) and GDM- (n=29) women. Infant weight and height at 2 months were obtained from the child health record. Z-scores were calculated. Results: Circulating Npalmitoylethanolamine (PEA) was higher in human milk of GDM+ women than in GDM- women (4.9 ± 3.2 vs. 3.3 ± 1.7, p=0.04). Higher levels were also found for several 2monoacyl-glycerols (2-MAGs) (p<0.05). The levels of NAEs (ß=-4.6, p=0.04) and especially non-omega-3 NAEs (B=-5.6, p=0.004) in human milk were negatively correlated with weight-for-age z-score of GDM+ offspring. Conclusion: The profile of eCBome mediators in human milk at 2 months postpartum was different in GDM+ compared to GDM- women and was associated with GDM+ offspring growth at 2 months. Clinical trial registration: ClinicalTrials.gov, identifier (NCT04263675 and NCT02872402).

Gestational Diabetes Mellitus, Human Milk Composition, and Infant Growth.

Background: Gestational diabetes mellitus (GDM) is known to affect human milk composition. Aims of this study were to compare macronutrient and energy content of human milk of women with (GDM+) and without GDM (GDM-), to assess the association between maternal health and human milk macronutrient and energy content and association between human milk macronutrient and energy content and infant growth. Study Design and Methods: Two months after delivery, hindmilk samples were collected. Triglyceride (TG), lactose, and protein content of human milk were measured. An oral glucose tolerance test was performed. Infant weight and length at birth and 2 months were collected. Weight-for-age (WAZ) and weight-for-length z-scores were calculated. Results: Twenty-four GDM+ and 29 GDM- women were included. Protein, lactose, and energy content of human milk were similar between groups. TG concentration was higher in GDM+ than in GDM- women (6.3 ± 2.0 versus 5.3 ± 1.2, p = 0.04). This difference was no longer significant after adjustment for maternal age and infant sex (p = 0.23). Maternal age was associated with TG (r = 0.28, p = 0.04) and lactose (r = -0.30, p = 0.03), while fasting glucose was associated with proteins (r = 0.30, p = 0.03) and tended to be associated with TG (r = 0.27, p = 0.05) and energy (r = 0.24, p = 0.08). TG levels in human milk were associated with weight (ß: 0.26, 95% confidence interval [CI]: 0.02 to 0.50) and WAZ (ß: 0.40, 95% CI: 0.05 to 0.75) at 2 months among children unexposed (GDM-) to GDM, but not among children exposed (GDM+) Conclusions: In conclusion, GDM status, maternal age, and fasting glucose level were associated with human milk composition. Finally, TG in human milk was associated with infant growth among GDM- children but not among GDM+ children. ClinicalTrials.gov NCT02872402.

Impact of selenium on the intestinal microbiome-eCBome axis in the context of diet-related metabolic health in mice.

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 Il1ß 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.