Agudelo Fredy Alexander Guevara, Leblanc Nadine, Bourdeau-Julien Isabelle, St-Arnaud Gabrielle, Dahhani Fadil, Flamand Nicolas, Veilleux Alain, Di Marzo Vincenzo, Raymond Frédéric
Centre Nutrition, santé et société (NUTRISS), and Institute of Nutrition and Functional Foods (INAF), Université Laval, Québec City, Québec, Canada.
Canada Excellence Research Chair on the Microbiome - Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Québec City, Québec, Canada.
FASEB J. 2025 Jul 15;39(13):e70763. doi: 10.1096/fj.202500934R.
Obesity is characterized by low-grade inflammation, changes in gut microbiota, and increased tone of the expanded endocannabinoid system (eCBome). The gut is a complex ecosystem that serves as an interface between the diet and its ultimate conversion to nutrients and energy for all cells of the organism. Manganese (Mn) is an essential micronutrient from the diet required for normal cell function and physiological processes. Moreover, it is an indispensable trace mineral for some microbial species since it is a cofactor in several metabolic enzymes. Therefore, we aimed to identify possible interactions between gut microbiota composition and the eCBome during dietary variations of Mn in the context of diet-induced obesity. Female and male mice were fed Mn-depleted and Mn-enriched diets in combination with Low Fat-Low Sucrose (LFLS) or High Fat-High Sucrose (HFHS) diets for 28 days to assess intestinal microbiota and eCBome levels. Mn-enriched diets enhanced the circulating levels of N-docosapentaenoyl-ethanolamine (DPEA) and anandamide (AEA), while they reduced the intestinal concentrations of other N-acylethanolamines, particularly in the caecum. Besides, we found a strong sex effect of Mn on the intestinal levels of 2-monoacylglycerols (2-MAGs), which were lower in females. Other endocannabinoid-like molecules involved in the immune response were impacted by dietary Mn enrichment, such as N-palmitoyl-glycine and N-oleoyl-L-serine. Concomitantly, Mn enrichment promoted segment-specific changes in the relative abundance of several taxa in intestinal microbiota following the HFHS diet. Microbial families such as Peptostreptococcaceae, Muribaculaceae, and Erysipelotrichaceae responded differentially to dietary variations in Mn. This study hints at potential interactions between Mn levels and diet composition with the eCBome and intestinal bacteria during dietary Mn variations within HFHS-induced dysmetabolic processes in a sex-dependent manner. These results will eventually contribute to identifying members of the gut microbiome and mediators of the eCBome useful for improving metabolic health.
肥胖的特征是低度炎症、肠道微生物群变化以及内源性大麻素系统（eCBome）扩张导致的张力增加。肠道是一个复杂的生态系统，它是饮食及其最终转化为生物体所有细胞的营养和能量之间的界面。锰（Mn）是饮食中正常细胞功能和生理过程所需的必需微量营养素。此外，它是一些微生物物种不可或缺的微量矿物质，因为它是几种代谢酶的辅助因子。因此，我们旨在确定在饮食诱导肥胖的背景下，锰饮食变化期间肠道微生物群组成与eCBome之间可能存在的相互作用。将雌性和雄性小鼠分别喂食缺锰和富锰饮食，并与低脂低蔗糖（LFLS）或高脂高蔗糖（HFHS）饮食组合，持续28天，以评估肠道微生物群和eCBome水平。富锰饮食提高了N-二十二碳五烯酰乙醇胺（DPEA）和花生四烯酸乙醇胺（AEA）的循环水平，同时降低了其他N-酰基乙醇胺的肠道浓度，尤其是在盲肠中。此外，我们发现锰对2-单酰甘油（2-MAGs）的肠道水平有很强的性别效应，雌性小鼠的2-MAGs水平较低。参与免疫反应的其他内源性大麻素样分子受到饮食中锰富集的影响，如N-棕榈酰甘氨酸和N-油酰-L-丝氨酸。与此同时，在HFHS饮食后，锰富集促进了肠道微生物群中几个分类群相对丰度的节段特异性变化。诸如消化链球菌科、毛螺菌科和丹毒丝菌科等微生物家族对锰的饮食变化有不同反应。这项研究表明，在HFHS诱导的代谢紊乱过程中，饮食中锰水平和饮食组成与eCBome和肠道细菌之间可能存在潜在的相互作用，且这种相互作用具有性别依赖性。这些结果最终将有助于确定对改善代谢健康有用的肠道微生物群成员和eCBome介质。
