The euphoria known as a “runner’s high” is caused by activation of the endocannabinoid system, a complex signaling system that regulates energy metabolism, inflammation, pain, and brain biology. The gut microbiota, which coordinates its activity with the brain and immune system, also modulates energy metabolism and inflammation and brain functions such as mood and cognition. Findings of a new report suggest that the endocannabinoid system is involved in communication between the gut and the immune system.

The gut microbiota, the community of microorganisms that live in the digestive tract, consume nutrients from the diet that are not absorbed by the host and produce multi-purpose compounds such as short chain fatty acids (SCFA). Previous research has demonstrated that some strains of bacteria that produce SCFAs modulate the number of cannabinoid and opioid receptors in the gut. A dysregulated endocannabinoid system and gut microbiota may increase the risk of inflammatory bowel disease, irritable bowel syndrome, and obesity; however, [exercise may improve microbiota and gut health.](​​https://www.hindawi.com/journals/omcl/2017/3831972/)

The authors collected baseline data from a group of 78 participants (age, greater than 45 years) with osteoarthritis who were part of a separate trial. They also collected data from a group of 40 additional adults. Participants provided a stool sample for the measurement of cannabinoids and cannabinoid metabolites, inflammatory markers, and SCFAs. They also sequenced the bacterial DNA contained in the stool sample to identify the types of bacteria present.

The researchers found that endocannabinoid concentrations in the stool increased as levels of SCFAs, SCFA-producing bacteria, and overall microbiota diversity increased. Higher endocannabinoid levels were associated with higher levels of inflammation-resolving cytokines such as interleukin-10 and lower levels of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha. Using a statistical model, the researchers found that endocannabinoid levels mediated the relationship between SCFA and inflammatory markers. This means that the relationship among these three variables is stronger than the relationship between SCFA and inflammatory markers alone.

These results demonstrate that endocannabinoids facilitate some of the anti-inflammatory effects of SCFAs and that the endocannabinoid system modulates the immune system through activity of the gut microbiota.

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• Watch this clip featuring Dr. Rhonda Patrick to learn more about how the gut microbiota regulates immune cells.