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The link between stress hormones and better digestive health

Researcher says understanding how cortisol acts will open doors to new treatments for those struggling with digestive issues.

For the first time, researchers from the National Institute of Health and Medical Research (Inserm) in France have suggested a link between cortisol and the plasticity of the intestinal nervous system—our “second brain.” 

Under the effect of cortisol, this network made up of 200 to 300 million neurons modifies the contractility of the muscles of the digestive tract, and of the colon in particular.

During a stressful event, cortisol secreted by the adrenal glands binds to a hormone receptor called “GR.” The couple then migrates into the nucleus, thus activating the transcription and expression of a gene which, at the end of the process, accelerates intestinal transit.

Better understanding how cortisol acts on the intestinal nervous system could open the door to new treatments, and possibly improve the quality of life of patients struggling with digestive disorders.

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Published in February 2023 in Frontiers in Neuroscience, these results represent a step forward for people struggling with pathologies involving a variation in cortisol levels, such as in the case of mental disorders. 

“We know that patients with psychiatric illnesses have extremely significant digestive disorders, as in autism for example,” explained Michel Neunlist, researcher at the head of the Enteric Nervous System in Digestive and Brain Diseases research laboratory at Inserm.

The use of an antagonist drug preventing the binding of cortisol to the GR receptors could be worth trying. “It will not directly save lives, but digestive disorders impact quality of life, anxiety, depression, which are central elements in the care of the patient,” says Neunlist.

Stress is also a triggering and aggravating factor for certain chronic diseases, such as obesity, multiple sclerosis, certain neurodegenerative and inflammatory bowel diseases. "Having a tool that blocks at a given time, during a stressful event, the implementation of this deleterious system can be quite interesting for occasional use over a short period of time.”

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This promising antagonist drug, however, still belongs to an uncertain future. “Classical pharmacological approaches would not lend themselves to this,” says Neunlist. “[Cortisol] regulates a lot of functions, both metabolic, immune and neuronal. It is a kind of molecular hub, hence the risk of blocking certain important functions by wanting to preserve a healthy intestinal transit.”

He says the research is still in its early stages as he is currently concentrating on understanding the common and specific mechanisms of the various pathologies linked to cortisol. A “softer” approach to countering the effects of the hormone would be to use gut microbiota modulators, such as probiotics.

The next major step in this cortisol study will be to move from experiments performed on mice to those on humans. "We have cured all the diseases in mice, and yet we still have human diseases," jokes Neunlist.

This is why the research unit he heads is working to develop tools to circumvent the differences between species. For example, he is working to reconstruct a human intestine from reprogrammed stem cells, in order to imitate the complex functions of our “second brain.” 

This article has been translated from its original French and first appeared on our sister site Profession Santé.

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