Longevity Briefs: How The Gut Microbiome Affects The Body’s Own ‘Cannabis’

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: Exercise can produce a feeling of euphoria, aka the ”runner’s high”. This is the result of the release of molecules called endocannabinoids which, as their name suggests, are similar to the active molecules found in the cannabis plant, and activate the same receptors within the body. The endocannabinoid system has been found to play a role in various biological processes including energy metabolism, inflammation and pain. We also know that exercise can affect these same systems by altering the composition of the gut microbiome, and we know that changes in the gut microbiome can affect the endocannabinoid system and vice-versa. Understanding this relationship in greater detail, such as which bacterial strains have the greatest impact on the endocannabinoid system, could prove beneficial for the treatment of inflammatory diseases.

What did the researchers do: In this study, researchers analysed data from two studies. In one, 78 people with knee osteoarthritis were recruited and split randomly into two groups. One group of 38 underwent 15 minutes of muscle strength training every day for six weeks, while the other group of 40 did not. In the other, researchers simply collected data from 35 healthy individuals who were not subject to any particular intervention. In both instances, blood and stool samples were collected at regular intervals, and information about gut microbiome composition, gene expression, endocannabinoid levels and inflammatory molecules was acquired.

Key takeaway(s) from this research: Participants who exercised had lower levels of inflammation and pain than the control group at the end of the study, and had significantly higher levels of three endocannabinoids called AEA, OEA and PEA. Increases in circulating endocannabinoids were associated with increased gut microbiome diversity, increased production of short-chain fatty acids (products of bacterial metabolism) by certain specific bacterial strains, and a reduction in inflammatory molecules. They also found that increased endocannabinoids were associated with increased expression of genes coding for receptors for short-chain fatty acids, and with a reduction in a pro-inflammatory strain of bacteria called Collinsella.

These associations were also found in the smaller cohort of healthy individuals, suggesting that they are generalisable to the general population. Based on these measured relationships, the researchers estimated that about a third of the anti-inflammatory effects of short-chain fatty acids produced by gut bacteria could be mediated by the endocannabinoid system. However, it’s also important to remember that these are all just statistical relationships that don’t prove causation – it’s still possible that exercise could have increased endocannabinoid levels through mechanisms unrelated to the gut microbiome.

Exercise therefore appears to exert its anti inflammatory effects partly through changes in gut microbiome composition, which in turn leads to a reduction in inflammation partly through the effects of short-chain fatty acids on the endocannabinoid system.

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