Supplemental Digital Content is Available in the Text.

Understanding changes to gut microbiota composition and metabolic output in response to acute exercise may be necessary for understanding the mechanisms mediating the long-term health and performance benefits of exercise. Our primary objective was to characterize acute changes in the fecal microbiome and metabolome following participation in an ultra-endurance (3.9km swim, 180.2km bike, 42.2km run) triathlon. An exploratory aim was to determine associations between athlete-specific factors (race performance [i.e., completion time] and lifetime years of endurance training) with pre-race gut microbiota and metabolite profiles. Stool samples from 12 triathletes (9M/3F; 43±14 yrs, 23±2 kg/m2) were collected ≤48 hours before and the first bowel movement following race completion. Intra- and inter-individual diversity of bacterial species and individual bacterial taxa were unaltered following race completion (P>0.05). However, significant reductions (P<0.05) in free and secondary bile acids (DCA, 12-ketoLCA) and short-chain fatty acids (butyric and pivalic acids), and significant increases (P<0.05) in long-chain fatty acids (oleic and palmitoleic acids) were observed. Exploratory analyses revealed several associations between pre-race bacterial taxa and fecal metabolites with race performance and lifetime history of endurance training (P<0.05). These findings suggest that 1) acute ultra-endurance exercise shifts microbial metabolism independent of changes to community composition and 2) athlete performance level and training history relate to resting-state gut microbial ecology.

Background and Purpose: Improved understanding of brain mechanisms regulating endogenous analgesia is important from a fundamental physiological perspective and for identification of novel therapeutic strategies for pain. The endocannabinoid system plays a key role in stress-induced analgesia, including fear-conditioned analgesia (FCA), a potent form of endogenous analgesia. Here, we studied the role of the endocannabinoid 2-arachidonoyl glycerol (2-AG) within the anterior cingulate cortex (ACC; a brain region implicated in the affective component of pain) in FCA in rats.Experimental Approach: FCA was modelled in male Lister-hooded rats by assessing formalin-evoked nociceptive behaviour in an arena previously paired with footshock.The effects of intra-ACC administration of MJN110 (inhibitor of monoacylglycerol lipase [MGL], the primary enzyme catabolizing 2-AG), AM630 (CB 2 receptor antagonist), AM251 (CB 1 receptor antagonist) or MJN110 + AM630 on FCA were assessed.Key Results: MJN110 attenuated FCA when microinjected into the ACC, an effect associated with increased levels of 2-AG in the ACC. This effect of MJN110 on FCA was unaltered by co-administration of AM251 but was blocked by AM630, which alone reduced nociceptive behaviour in non-fear-conditioned rats. RT-qPCR confirmed that mRNA encoding CB 1 and CB 2 receptors was detectable in the ACC of formalin-injected rats and unchanged in those expressing FCA. Conclusion and Implications:These results suggest that an MGL substrate in the ACC, likely 2-AG, modulates FCA and that within the ACC, 2-AG-CB 2 receptor signalling may suppress this form of endogenous analgesia. These results may facilitate increased understanding and improved treatment of pain-and fear-related disorders and their co-morbidity. analgesia is a potent form of endogenous analgesia and a useful model with which to study the neurobiological mechanisms underpinning endogenous pain suppression and fear-pain interactions.The endocannabinoid system consists of cannabinoid 1 (CB 1 ) and cannabinoid 2 (CB 2 ) receptors, their endogenous ligands, anandamide and 2-arachidonoylglycerol (2-AG), and their key catabolizing enzymes, fatty acid amide hydrolase and monoacylglycerol lipase (MGL). The endocannabinoid system has been shown to play a key role in the expression of fear-conditioned analgesia (Finn et al.