Plasma Levels of Endocannabinoids and Their Analogues Are Related to Specific Fecal Bacterial Genera in Young Adults: Role in Gut Barrier Integrity

Abstract

Objective: To investigate the association of plasma levels of endocannabinoids with fecal microbiota. Methods: Plasma levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as well as their eleven analogues, and arachidonic acid (AA), were measured using liquid chromatography-tandem mass spectrometry in 92 young adults. DNA extracted from stool samples was analyzed using 16S rRNA gene sequencing. Lipopolysaccharide levels were measured in plasma samples. Results: Plasma levels of endocannabinoids and their analogues were not related to beta or alpha diversity indexes. Plasma levels of AEA and related N-acylethanolamines correlated positively with the relative abundance of Faecalibacterium genus (all rho ≥ 0.26, p ≤ 0.012) and Akkermansia genus (all rho ≥ 0.22, p ≤ 0.036), and negatively with the relative abundance of Bilophila genus (all rho ≤ −0.23, p ≤ 0.031). Moreover, plasma levels of 2-AG and other acylglycerols correlated positively with the relative abundance of Parasutterella (all rho ≥ 0.24, p ≤ 0.020) and Odoribacter genera (all rho ≥ 0.27, p ≤ 0.011), and negatively with the relative abundance of Prevotella genus (all rho ≤ −0.24, p ≤ 0.023). In participants with high lipopolysaccharide values, the plasma levels of AEA and related N-acylethanolamines, as well as AA and 2-AG, were negatively correlated with plasma levels of lipopolysaccharide (all rho ≤ −0.24, p ≤ 0.020). Conclusion: Plasma levels of endocannabinoids and their analogues are correlated to specific fecal bacterial genera involved in maintaining gut barrier integrity in young adults. This suggests that plasma levels of endocannabinoids and their analogues may play a role in the gut barrier integrity in young adults.

Sex differences in endocannabinoids during 3 years of Mediterranean diet intervention: Association with insulin resistance and weight loss in a population with metabolic syndrome

“…The mechanism underlying the observed sex-specific associations between NAEs and weight loss could be related to the interplay between eCBs or NAEs, insulin resistance and gut intestinal barrier integrity ( 33 ). Accordingly, plasma concentrations of eCBs and NAEs have been related with the gut barrier integrity ( 83 ), and insulin signaling has been identified as an essential gatekeeper of intestinal barrier integrity ( 84 ). Therefore, those women with lower insulin resistance could have a healthier intestinal barrier and a better NAEs profile, and could be more susceptible to dietary-induced weight loss changes.…”

Microbial Dysbiosis Linked to Metabolic Dysfunction-Associated Fatty Liver Disease in Asians: Prevotella copri Promotes Lipopolysaccharide Biosynthesis and Network Instability in the Prevotella Enterotype

“…Nevertheless, Francisco et al propose a plausible association between an abundance of P. copri and an elevated risk of insulin resistance [10]. Additionally, Prevotella can generate higher levels of endotoxin lipopolysaccharide (LPS), a component of bacterial outer membranes [11]. Elevated LPS levels may enter the bloodstream, triggering inflammation and fostering the development of MAFLD [12].…”