Exercise reduces inflammation through endocannabinoids and gut bacteria

The processes through which exercise reduces inflammation have been revealed in new research.
  • Endogenous cannabinoids, or cannabis-like substances produced by the body, are important regulators of metabolism and inflammation.
  • When dietary fiber is broken down, microorganisms in the gut, collectively known as the gut microbiota, create short-chain fatty acids.
  • Experts know that endogenous cannabinoids, as well as the short-chain fatty acids produced by the gut microbiota, have anti-inflammatory properties.
  • According to a new study, a 6-week exercise intervention decreased inflammatory marker levels while also increasing endocannabinoid and short-chain fatty acid levels.
  • These findings imply that gut bacteria’s short-chain fatty acids may interact with endocannabinoids to elicit anti-inflammatory effects.

Cannabis binds to cannabinoid receptors in the body to produce its effects. These cannabinoid receptors also bind to endocannabinoids, which are endogenous cannabinoids produced by the body.

Endocannabinoids play a role in a variety of biological processes, including metabolism, pain, inflammation, and brain information transmission. The release of endocannabinoids, along with opioids, is also responsible for the euphoria that most people feel after a strenuous workout.

According to a new study, everyday physical activity is useful in decreasing inflammation-related indicators. Furthermore, the study implies that the endocannabinoid system may work in tandem with gut microbes to reduce inflammatory indicators.

The study, which was published in the journal Gut Microbes, was led by researchers from the University of Nottingham.

Endocannabinoids and gut microbes

Cannabinoid receptors are found in the brain, peripheral nervous system, and immune system, and endocannabinoids bind to them. Cannabinoid receptors are also found in the enteric nervous system, which controls the gut.

Obesity and metabolic diseases are linked to disruption of the endocannabinoid system.

Microorganisms in the gut, referred to collectively as the gut microbiota, also have a substantial impact on metabolism. Obesity and other metabolic problems are linked to changes in the makeup of these bacteria, including a reduction in the diversity of gut microbes.

The endocannabinoid system appears to interact with the gut microbiota to regulate metabolism and energy homeostasis, according to research.

The nature of the gut bacteria, for example, can affect the quantities of endocannabinoids and cannabinoid receptors in the intestine. Obesity leads to alterations in gut microbiota composition as well as reduced endocannabinoid levels.

Chronic, low-grade inflammation is linked to obesity and other metabolic problems. Both endocannabinoids and the gut microbiota have a role in inflammation modulation, which includes the aforementioned disorders.

Short-chain fatty acids are produced when certain gut bacteria species break down dietary fiber. These short-chain fatty acids have been linked to reduced inflammation and may have anti-obesity properties.

Similarly, the endocannabinoid system can help to reduce inflammation, and alterations in the endocannabinoid system have been linked to IBS and obesity.

Looking at the mechanism

Scientists aren’t sure if the short-chain fatty acids produced by gut microbes interact with the endocannabinoid system to create anti-inflammatory effects.

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

Exercise is linked to higher endocannabinoid levels and anti-inflammatory benefits over time. The researchers employed a 6-week exercise intervention to look at the link between endocannabinoids, inflammation, and gut microorganism-produced short-chain fatty acids.

Physical activity was linked to lower inflammation, as well as increased levels of short-chain fatty acids and endocannabinoids, according to the researchers.

Dr. Amrita Vijay, a research associate at the University of Nottingham and the study’s first author, told Medical News Today:

“The findings from the current study highlight that simple lifestyle interventions such as exercise can modulate endocannabinoids, and this is a timely discovery, especially in the time when there is increasing interest around the use of cannabidiol and other related supplements in reducing levels of inflammation.”

Study design

There were two cohorts in this study. The first cohort included 78 persons over the age of 45 who were living in a community setting and had knee arthritis.

At the start of the study, the researchers looked at the link between the endocannabinoid system, gut microbiota, and inflammation in this group. They followed up with a second cohort of 35 people over the age of 18 to validate their findings.

In the first group, the researchers looked at how a 6-week exercise program customized to people with osteoarthritis affected the link between the endocannabinoid system, inflammation, and gut microbiota. They did this by dividing the participants into two groups: a treatment group of 38 people and a control group of 40 people.

The researchers measured the levels of endocannabinoids, short-chain fatty acids, and inflammatory markers in the subjects’ blood. Cytokines, a type of immune protein that has either pro-inflammatory or anti-inflammatory activities, were among the inflammatory indicators.

The researchers employed stool samples and DNA sequencing to determine the abundance of different gut microbiota species.

Inflammation, endocannabinoids, and gut microbiota

The researchers discovered that endocannabinoid levels had a positive link with gut microbial diversity, short-chain fatty acid levels, and levels of gut microbiota species that produce these short-chain fatty acids before the start of the exercise intervention in the first group.

Higher endocannabinoid levels, on the other hand, were connected to reduced levels of Collinsella, a gut bacteria genus linked to inflammation.

Endocannabinoid levels were favorably connected with anti-inflammatory cytokines but had a negative connection with pro-inflammatory cytokines, confirming these findings. The first cohort’s results were comparable to those acquired by the team in the second cohort.

The researchers then calculated the role of endocannabinoids in mediating short-chain fatty acid anti-inflammatory actions. They utilized a statistical method known as mediation analysis to determine the extent to which a third factor mediates the association between two variables.

Endocannabinoids were discovered to be responsible for nearly one-third of the effects of short-chain fatty acids on inflammatory indicators. This shows that, in addition to the endocannabinoid system, other biological components or pathways may be involved in mediating the anti-inflammatory effects of short-chain fatty acids produced by the gut bacteria.

Similarly, the researchers looked into how short-chain fatty acids controlled endocannabinoids’ anti-inflammatory effects. Short-chain fatty acids were thought to be responsible for around half of the effects.

The authors do warn, however, that estimations generated through mediation analysis may not imply causality.

Exercise’s Effects

The researchers then looked at how the 6-week exercise intervention affected the relationship between endocannabinoids and short-chain fatty acid levels, gut microbiome composition, and inflammatory markers on the one hand, and endocannabinoids and short-chain fatty acid levels, gut microbiome composition, and inflammatory markers on the other.

The exercise group’s endocannabinoid and short-chain fatty acid levels increased, whereas the control group’s levels remained same. At the same time, the level of pro-inflammatory cytokines in the exercise group decreased.

After 6 weeks, changes in the endocannabinoid anandamide were linked with changes in the short-chain fatty acid butyrate in both groups. Furthermore, the study discovered a link between changes in endocannabinoid levels and an increase in the population of bacteria that produce short-chain fatty acids.

Changes in endocannabinoid levels, on the other hand, were adversely connected to changes in the number of bacteria and cytokines linked to pro-inflammatory effects.

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

The short-chain fatty acid receptor is linked to a reduced risk of obesity, while CNR2 has anti-inflammatory properties.

These findings show that an interaction between endocannabinoids and short-chain fatty acids may be involved in the anti-inflammatory benefits of physical activity.

Strengths and limitations

Highlighting the study’s salience, Dr. Vijay said, “The findings are novel, as we may have found a key link between how substances produced by gut microbes interact with the substances produced by our own bodies, which tell us how physical exercise reduces inflammation.”

The authors emphasize that their findings are purely observational and do not prove causation. Furthermore, Dr. Vijay added, “The exercise intervention we carried out was performed in individuals with painful knee osteoarthritis and may not be directly relevant to other groups.”

“It would be interesting to test if different forms of exercise have different effects on our bodies in relation to the levels of these substances being produced and thereby influencing inflammation. It is also important to consider the effect of diet on these relationships.”

– Dr. Vijay