Exercise May Reduce Inflammation By Raising Endocannabinoids

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New research sheds light on the mechanisms by which exercise reduces inflammation. Artem Varnitsin / EyeEm / Getty Images
  • Endogenous cannabinoids, which the body produces, are cannabis-like compounds that play an important role in modulating metabolism and inflammation.
  • Microorganisms in the gut, collectively known as the gut microbiota, produce short-chain fatty acids when breaking down dietary fiber.
  • Experts know that endogenous cannabinoids have anti-inflammatory effects, as do short-chain fatty acids produced by the gut microbiota.
  • A new study reports that a 6-week exercise intervention reduced levels of inflammatory markers and that this effect was accompanied by higher levels of endocannabinoids and short-chain fatty acids.
  • These results suggest that short-chain fatty acids produced by intestinal microorganisms may interact with endocannabinoids to exert anti-inflammatory effects.

Cannabis exerts its effects on the body by binding to cannabinoid receptors. These cannabinoid receptors also bind to endogenous cannabinoids that the body makes, called endocannabinoids.

Endocannabinoids are involved in the modulation of many biological processes, including metabolism, pain, inflammation, and the transmission of information in the brain. The release of endocannabinoids, along with opioids, is also responsible for the feeling of euphoria that people typically experience after intense training.

A new study has shown that daily physical exercise is effective in lowering the levels of markers linked to inflammation. Additionally, the study suggests that the endocannabinoid system may interact with intestinal microorganisms to produce such a reduction in inflammatory markers.

Researchers at the University of Nottingham led the research, which appears in the journal Intestinal microbes.

Endocannabinoids bind to cannabinoid receptors found in the brain, the peripheral nervous system, and the immune system. The enteric nervous system, which controls the gut, also expresses cannabinoid receptors.

Deregulation of the endocannabinoid system is associated with obesity and metabolic disorders.

Microorganisms in the gut, which people collectively call the gut microbiota, also have a significant influence on metabolism. Changes in the composition of these microorganisms, including reduction in the diversity of intestinal microorganisms, are associated with obesity and other metabolic disorders.

Studies suggest that the endocannabinoid system interacts with the gut microbiota to influence metabolism and energy homeostasis.

For example, the composition of the gut microbiota can influence the levels of endocannabinoids and cannabinoid receptors in the gut. Specifically, changes in the composition of the gut microbiome in obesity occur alongside lower endocannabinoid levels.

Obesity and other metabolic disorders are also associated with chronic low-grade inflammation. Both endocannabinoids and the gut microbiota are involved in the modulation of inflammation, including under the aforementioned conditions.

Some species of gut bacteria can break down dietary fiber to produce short-chain fatty acids. These short-chain fatty acids are linked to lower inflammation and may exert protective effects against obesity.

Likewise, the endocannabinoid system can limit inflammation, and changes in the endocannabinoid system are seen in irritable bowel syndrome (IBS) and obesity.

Scientists do not fully understand whether the short-chain fatty acids produced by intestinal microorganisms can interact with the endocannabinoid system to produce anti-inflammatory effects.

The present study reports that the endocannabinoid system may mediate, in part, the anti-inflammatory effects of short-chain fatty acids produced by the gut microbiota, and vice versa.

Exercise is associated with increased endocannabinoid levels and long-term anti-inflammatory effects. The researchers used a 6-week exercise intervention to further investigate the association between endocannabinoids, inflammation, and short-chain fatty acids produced by microorganisms in the gut.

Researchers found that exercise was associated with lower inflammation, accompanied by higher levels of short-chain fatty acids and endocannabinoids.

The study’s first author, Dr Amrita Vijay, associate researcher at the University of Nottingham, said Medical News Today:

“The results of the present study underscore that simple lifestyle interventions such as exercise can modulate endocannabinoids, and this is a timely discovery, particularly at a time when the use of cannabidiol and others. There is growing interest in related supplements to reduce inflammation levels. ”

The present study involved two cohorts. The first cohort consisted of 78 adults over the age of 45, living with arthritis of the knee and residing in a community setting.

The researchers looked at the relationship between the endocannabinoid system, gut microbiota, and inflammation in this baseline cohort. They then confirmed these results in a second cohort made up of 35 individuals over 18 years of age.

The researchers also evaluated the effects of a 6-week exercise intervention tailored for people with osteoarthritis on the relationship between the endocannabinoid system, inflammation, and gut microbiota in the first cohort. To do this, they divided the participants into a treatment group, consisting of 38 participants, and a control group, involving 40 people.

The researchers used blood samples from the participants to assess serum levels of endocannabinoids, short-chain fatty acids, and inflammatory markers. The inflammatory markers included cytokines, a class of immune proteins that have pro-inflammatory or anti-inflammatory effects.

The team used stool samples and performed DNA sequencing to assess the abundance of various species in the gut microbiota.

Prior to the start of the exercise intervention in the first cohort, researchers found that endocannabinoid levels positively correlated with gut microbial diversity, short-chain fatty acid levels, and species levels. of the gut microbiota that produce these short-chain fatty acids.

In contrast, higher endocannabinoid levels were associated with lower levels of Collinsella, a kind of intestinal bacteria linked to increased inflammation.

Consistent with these results, endocannabinoid levels were positively correlated with levels of anti-inflammatory cytokines, but had a negative relationship with levels of pro-inflammatory cytokines. These results from the first cohort were similar to those the team obtained from the second cohort.

The researchers then estimated the contribution of endocannabinoids to mediate the anti-inflammatory effects of short-chain fatty acids. They used a statistical method called mediation analysis, which can help estimate how much a third factor plays a role in mediating the relationship between two variables.

They found that endocannabinoids mediate about a third of the effects of short-chain fatty acids on inflammatory markers. This suggests that other factors or biological pathways, in addition to the endocannabinoid system, may play a role in mediating the anti-inflammatory effects of short-chain fatty acids produced by the gut microbiome.

Likewise, researchers investigated the extent to which short-chain fatty acids altered the effects of endocannabinoids on inflammation. They estimated that short chain fatty acids mediate about half of these effects.

However, the authors caution that such estimates, which they obtained using mediation analysis, do not imply causation.

Next, the researchers examined how the 6-week exercise intervention affected the association between endocannabinoid levels on the one hand and levels of short-chain fatty acids, gut microbiome makeup, and inflammatory markers. on the other hand.

They found that the levels of endocannabinoids and short-chain fatty acids increased in the exercise group, but showed no change in the control group. At the same time, there was a decrease in the level of pro-inflammatory cytokines in participants in the exercise group.

The changes in the levels of the endocannabinoid anandamide correlated with the short-chain fatty acid butyrate after 6 weeks in both groups. In addition, the researcher found a positive correlation between changes in endocannabinoid levels and the increased abundance of bacteria producing short-chain fatty acids.

On the other hand, changes in endocannabinoid levels were negatively correlated with changes in the abundance of bacteria and cytokines associated with pro-inflammatory effects.

Finally, endocannabinoid levels were positively associated with gene expression levels for the short-chain fatty acid receptor FFAR2 and the cannabinoid receptor CNR2.

The short-chain fatty acid receptor is associated with a lower risk of obesity, while CNR2 is associated with anti-inflammatory effects.

These results suggest that the anti-inflammatory effects resulting from physical exercise could potentially involve an interaction between endocannabinoids and short-chain fatty acids.

Emphasizing the importance of the study, Dr Vijay said: “The results are new, as we may have found a key connection between how substances produced by gut microbes interact with substances produced by our own. bodies, which tell us how exercise reduces inflammation. ”

The authors note that their results are observational and do not establish a causal link. Further, Dr Vijay added, “The exercise intervention we performed was performed in people with painful osteoarthritis of the knee and may not be directly relevant for other groups.

“It would be interesting to test whether different forms of exercise have different effects on our body depending on the levels of these substances produced and thus influencing inflammation. It is also important to consider the effect of diet on these relationships.

– Dr Vijay

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