Diet and Gut Microbiota Primarily Influence Fecal Endocannabinoidome Mediators

Overview

This study characterizes the profile of endocannabinoidome (eCBome) mediators in human feces and identifies diet and gut microbiota composition as primary determinants. Fecal levels of certain eCBome mediators correlate weakly with circulating levels but are strongly associated with dietary fiber intake, unsaturated fatty acids, and gut microbiota diversity.

Background

The endocannabinoidome (eCBome) comprises signaling lipids such as N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) involved in energy homeostasis and inflammation. These mediators act through multiple receptors and are present in various tissues and biological fluids including feces. Previous research has linked circulating eCBome mediators with adiposity and diet, but the determinants of fecal eCBome mediators remain unclear. Understanding how diet and gut microbiota influence fecal eCBome profiles is important for metabolic and intestinal health management.

Data Highlights

Key Findings

• Six NAEs and seven 2-MAGs were identified in human feces, with omega-3–derived mediators often undetectable.
• Fecal eCBome mediator levels correlate weakly but positively with circulating plasma levels.
• Fecal levels of 2-arachidonoyl-glycerol, N-palmitoyl-ethanolamine, and N-docosahexaenoyl-ethanolamine are positively associated with visceral adiposity and metabolic parameters.
• Higher dietary fiber intake is linked to lower fecal concentrations of several eCBome mediators.
• Intakes of unsaturated fatty acids correlate with increased fecal 2-oleoyl-glycerol and 2-linoleoyl-glycerol levels.
• Gut microbiota diversity and composition are strong correlates of the fecal eCBome mediator profile, suggesting a bidirectional relationship.

Clinical Implications

These findings highlight the importance of diet, particularly fiber and unsaturated fatty acid intake, in modulating fecal eCBome mediator profiles, which may influence host metabolic and intestinal health. The strong association with gut microbiota composition suggests potential therapeutic targets through microbiome modulation to regulate eCBome signaling pathways involved in energy homeostasis and inflammation.

Conclusion

The fecal endocannabinoidome mediator profile is primarily shaped by diet and gut microbiota rather than circulating levels, underscoring a complex interplay between host metabolism, diet, and microbial ecology in regulating eCBome signaling.

References

1. Manca et al. 2023 -- The Profile of Endocannabinoidome Mediators in Human Feces Is Primarily Influenced by Diet and Gut Microbiota