Seasonal variations in circulating endocannabinoidome mediators and gut microbiota composition in humans

Abstract

Background: The human gut microbiome-endocannabinoidome axis is crucial for several homeostatic processes, including inflammation and energy metabolism, and is influenced by many endogenous and exogenous factors, such as dietary habits. Changes in the gut microbiome in response to seasonal variations were previously reported and tentatively attributed to shifts in dietary patterns. However, there is a need for longitudinal studies in industrialized populations to comprehensively explore seasonal variations independently of lifestyle confounding factors. Objective: To investigate the longitudinal effects of seasonal variations on the composition of the gut microbiome and the circulating levels of endocannabinoidome mediators in humans, while elucidating the contributing factors underlying these changes. Methods: Plasma and fecal samples were collected at the end of both the winter and summer in a longitudinal cohort of 48 individuals living in Québec City (Canada). Dietary habits, medical history, fecal microbiota taxonomic composition and plasma levels of circulating N‑acyl‑ethanolamines (NAEs) and 2‑monoacyl-glycerols (2‑MAGs) were obtained at each time point. Results: Lower circulating levels of most NAEs were observed at the end of summer. These changes were accompanied by a reduction in the relative abundance of the Bifidobacteriaceae and Lachnospiraceae families, along with an increase in the abundance of the Bacteroidaceae and Ruminococcaceae families. These seasonal variations were not associated with concurrent changes in adiposity parameters, dietary intakes, physical activity habits, or vitamin D status. Importantly, the magnitude of the shift in gut microbiota composition from winter to summer was found to be associated with the seasonal variations in circulating endocannabinoidome (eCBome) mediators. Conclusion: This study identified specific seasonal changes in gut microbiota composition and circulating levels of several NAEs, which were not associated with vitamin D status and lifestyle habits. It underscores the importance of the gut microbiota-endocannabinoidome axis in the pathophysiology of seasonal changes, and of considering seasons in clinical trials on these systems.