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Université Laval researchers are studying how the endocannabinoidome and gut microbiome influence your health.

Obesity and lifestyle factors, including inactivity, smoking and stress can contribute to the development of metabolic syndrome; a cluster of conditions that occur together, increasing your risk of heart disease, stroke and type 2 diabetes. These conditions include elevated blood pressure, high blood sugar and high cholesterol levels.

As part of an international team, Université Laval researchers Vincenzo Di Marzo and Cristoforo Silvestri are studying how lifestyle interventions may improve the functioning of our microbiome and endocannabinoidome – leading to better health.  Dr. Di Marzo holds the Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health and leads a Joint International Research Unit co-funded with the Italian National Research Council (CNR). Dr. Silvestri leads the Sentinel North Partnership Research Chair on the Gut Microbiome-Endocannabinoid System as an Integrator of Extreme Environmental Influences on Bioenergetics.

They are part of Sentinel North, a major interdisciplinary research and training program that supports over 700 researchers and students from 40 Université Laval departments working in a spirit of convergence and innovation with northern partners, public and private sector organizations, as well as other universities and research institutes in more than 20 countries. Sentinel North aims to shed light on the northern environment and its impact on humans through innovative technologies and interdisciplinary research in support of sustainable health and development.

How the endocannabinoidome and microbiome influence health

Cannabis has more than 100 compounds that are known as cannabinoids. These cannabinoids bind to receptors found throughout the human body. Work on these receptors identified two lipids produced by our bodies that while structurally unrelated to cannabinoids, were found to bind to the receptors of the main psychoactive cannabinoid, THC, and stimulate their activity. These lipids were thus called endocannabinoids. The endocannabinoids and their receptors are found throughout our organs, immune system and nervous system and have a huge impact on our health. Other cannabinoids instead modulate the activity of other receptors activated by endogenous analogues of the endocannabinoids, which together constitute an expanded endocannabinoid system, or endocannabinoidome. Our bodies also have trillions of microbes, including bacteria, fungi and viruses, collectively known as the microbiome. These microbes, with the largest numbers in our gut, also have a major influence on our health, which can either be beneficial or place us at greater risk for disease.

“We have to think of our bodies as a planet for microorganisms, with many different ecosystems. When we take in food or medicine, we may be changing these ecosystems and hence their microbiomes, with their thousands of species; the same with the host endocannabinoidome, with its hundreds of receptors, lipid signals and enzymes. The two systems are affecting each other and responding to similar physiological, pathological and environmental (such as nutritional and lifestyle) changes,” says Dr. Silvestri.

For example, high intake of linoleic acid has shown to lead to harmful overactivity of some endocannabinoidome signals, while omega-3 fatty acids reverse this effect and enhance the signaling of other endocannabinoidome members, which are more beneficial to metabolic health. Similar effects were found on the gut microbiome.

The endocannabinoidome-microbiome axis is a mechanism through which lifestyle choices affect various aspects of metabolism and may lead to metabolic syndrome when dysregulated. From Di Marzo, V.; Silvestri, C. Lifestyle and Metabolic Syndrome: Contribution of the Endocannabinoidome. Nutrients 2019, 11, 1956. https://doi.org/10.3390/nu11081956

Northern population affected by environmental factors

In addition to nutrition and other lifestyle factors, our environment, such as exposure to pollutants or extreme temperatures, can affect the endocannabinoidome and microbiome, with an impact on metabolic health. Climate change and modernisation are having major impacts on the environment and lifestyles of northern populations that can be disproportionately affected by such factors.

“Of particular relevance to those living in the North is the role of stress caused by environmental factors, like alternating periods of light and dark,” says Dr. Silvestri, adding that indigenous northern populations are also facing a decrease in consumption of country foods that include fish, seals, and whales, which are excellent sources of omega-3 fatty acids.

“These sources of food are also accumulators of environmental pollutants,” he says. “Modern society is contaminating an extremely rich dietary source of essential factors for metabolic health on which northern populations have relied. Switching away from those traditional foods has been associated with increased susceptibility to metabolic syndrome.” To help northern populations and people all over the world, the team wants to demonstrate the cause-and-effect relationship between the endocannabinoidome and the gut microbiome. For example, when they altered endocannabinoid levels in a mouse model, it caused changes in its gut microbiome and its ability to respond to a high-calorie, processed diet; conversely, when they took away the gut microbiome from mice, this deeply altered their endocannabinoidome.

Dr. Di Marzo says that the team hopes to demonstrate that the endocannabinoidome is part of the system through which the gut microbiome communicates with its host (your body). “Then we can think of manipulating the endocannabinoidome and gut microbiome in a coordinated manner through lifestyle interventions, such as nutrition, or personalised medications, to treat metabolic syndrome and improve health.”

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