Intestinal dysbiosis, depression, and endocannabinoid system

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We live inside each of us there are hundreds of species of bacteria that make up the intestinal microbiome, which has a huge impact on our well-being, affecting many physiological processes, including our immunity, metabolism and neurological function. Medical scientists have shown that an imbalance in the intestinal microbiome, known as dysbiosis, can lead to depression and other adverse health outcomes. But the specific molecular pathways that link intestinal dysbiosis to mood disorders are still largely unknown territory.

A recent one report by French scientists in Barcelona Communications on Nature (Chevalier, 2020) opens new avenues by exploring how the endocannabinoid system mediates the impact of the intestinal microbiota on mood and brain function. This article is based on previous research on the pathophysiology of depression that focuses on changes in the hippocampus, an area of ​​the brain where cannabinoids (CB1) concentrate the receptors.

CB1 receptors regulate neurogenesis – the creation of new brain cells – in the hippocampus. I the reduction of hippocampal neurogenesis in the adult brain it is considered a hallmark of clinical depression.

Several studies indicate this activation of CB1 receptor signaling produces antidepressant effects by stimulating neurogenesis in the hippocampus. Tetrahydrocannabinol (THC) i cannabidiol (CBD) are neurogenic compounds that promote the formation of neurons in the adult brain. Physics exercise it also increases neurogenesis by preparing the endocannabinoid system, while chronic stress has the opposite effect.

Chronic stressIt has been shown that a risk factor for many diseases decreases cannabinoid signaling and neurogenesis in the brain. Alterations of the intestinal microbiota composition after chronic stress is also well documented.

Mouse poop

In an effort to shed light on the mechanisms by which chronic stress induces dysbiosis, researchers at the Institut Pasteur in Paris transplanted the intestinal microbiota from a stressed depressed mouse to naive, stress-free mice. Naive mice that received the stool transplant became anxious and exhibited depressive behavior, such as the donor mouse.

In addition, fecal dysbiotic transplantation of the mouse with chronic stress resulted in a reduction in neurogenesis in the hippocampus of the recipient mouse. And reduced neurogenesis in the adult hippocampus was associated with dysregulation of the endocannabinoid system in the brain of the recipient rodent. These changes were not seen in laboratory animals that received a “microbiota control” transplant from a normal, strain-free mouse.

In addition, French scientists found that dysbiotic fecal transplantation altered the fatty acid metabolism of recipient mice, leading to a “systemic decrease in endocannabinoid precursors.”

Specifically, the researchers identified a lack of diacylglycerol (DAY) compounds, which are an essential element of 2-AG [2-Arachidonoyglycerol], the most prevalent endocannabinoid in the brain and body.

“In the hippocampus, we observed a decrease of 2-AG“In mice that received the dysbiotic fecal transplant” but not with control microbiota, “according to the French team, which noted that serum levels of DAY “They were inversely correlated with the severity of depressive behaviors.” Sold out DAY means less 2-AG, decreased cannabinoid receptor activity, and more intense mood disorders.

The stool transplant experiment showed that “the intestinal microbiota [are] enough to initiate a pathological feeding loop for depressive disorders affecting the endocannabinoid system of the hippocampus, a brain region strongly involved in the development of depressive symptoms ”.

Lactobacilli & Endocannabinoid precursors

Medical researchers have identified key changes in the microbiome that contribute to intestinal dysbiosis. Mouse-related fecal transfer data revealed that stress-induced “intestinal bacterial composition disturbances” were characterized by loss of Lactobacilli, an alteration that persisted after microbiota transplantation into naive hosts. “Beyond animal models, intestinal microbiota dysbiosis is characterized by low Lactobacilli frequency has also been detected in depressed humans.

The next step was obvious: determine if probiotic treatment with Lactobacilli improved depressive behavior in mice that received a dysbiotic fecal transplant. Indeed, that did the trick. A Lactobacillus The strain has been shown to relieve microbiota-induced anxiety and depression, while increasing endocannabinoid brain levels and hippocampal neurogenesis. “We have found one of the mechanisms by which Lactobacilli promoting these effects is by regulating the bioavailability of endocannabinoid precursors, ”the French study stated.

This finding adds a new dimension to the significant body of scientific literature, which proves what “Lactobacilli treatment, as well as the administration of other probiotics, are beneficial in significantly reducing depression and anxiety scores in patients. “

It is reasonable to postulate that, in addition to probiotic intervention, a diet rich in endocannabinoid precursor compounds, such as arachidonic acid, will increase 2-AG levels in the brain. Milk and meat are rich sources of arachidonic acid, which it combines with DAY create 2-AG. (I’m sorry, vegans, but that’s what science says.) 2-AG is activated CB1 cannabinoid receptors in the brain, and this produces anxiolytic and antidepressant effects by modulating hippocampal neurogenesis in humans and laboratory animals.

A key path

Of course, there are other ways to improve your cannabinoid tone. Consumption of resin-rich cannabis is a popular and time-tested option. But this was not the focus of the French study, which identified what appears to be a key pathway linking microbiota dysbiosis with mood disorders.

“In summary,” the authors conclude, “our data show that microbiota dysbiosis induced by chronic stress affects lipid metabolism and endocannabinoid generation, leading to decreased signaling of the endocannabinoid system and a reduced adult neurogenesis in the hippocampus … interrupt this pathological feeding loop by administering arachidonic acid or Lactobacillus probiotic strain, our study supports the concept that dietary or probiotic interventions can be effective levers in the therapeutic arsenal to combat stress-associated depressive syndromes. “


Martin A. Lee is the Project Director CBD and the author of Smoke Signals: The Social History of Marijuana: Medical, Recreational, and Scientific.


Copyright, project CBD. Cannot reprint without permission.




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