Ultra-Endurance triathlon competition shifts fecal metabolome independent of changes to microbiome composition.

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 (3.9 km swim, 180.2 km bike, 42.2 km 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 (9 males/3 females; 43 ± 14 yr, 23 ± 2 kg/m2) were collected ≤48 h 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 [deoxycholic acid (DCA), 12-keto-lithocholic acid (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.NEW & NOTEWORTHY This is the first study to characterize acute changes in gut microbial ecology and metabolism following an ultra-endurance triathlon. We demonstrate changes in gut microbial community function, but not structure, as well as several associations between gut microbiome and fecal metabolome characteristics with race completion time and lifetime history of endurance training. These data add to a small but growing body of literature seeking to characterize the acute and chronic effects of exercise on the gut microbial ecosystem.

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

ABSTRACT: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.

Attenuation of fear-conditioned analgesia in rats by monoacylglycerol lipase inhibition in the anterior cingulate cortex: Potential role for CB2 receptors.

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 (CB2 receptor antagonist), AM251 (CB1 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 CB1 and CB2 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-CB2 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.