Gut-Brain Axis

Gut-Brain Axis

Up until recently, scientists had minimal understanding of how our GI tract and brain are connected.  Until this new research I naively figured the only connection was my tummy telling my brain when I was hungry.  As it turns out there is a very strong bidirectional interplay between the brain and the GI tract and a major fulcrum is the gut microbiome.  The ENS (enteric (GI) nervous system) interacts with the intestinal membrane and its immune cells.  Changes in the membrane and immune cells are mediated by local hormones and neuroactive molecules.  These, in turn, affect the local nerves which send messages to the brain.  And the brain sends messages back. 

The importance of these connections has led to better understanding of both GI problems and neurologic disorders.   For instance, these is mounting evidence that altered GI microbiome plays a role in anxiety, depression, OCD behavior, autism, Parkinson’s disease, Alzheimer’s disease, and others.  On the other side of the equation is greater understanding of how the brain contributes to irritable bowel syndrome and inflammatory bowel disease. 

The ENS is often referred to as the second brain because of its size (100 million neurons and 400 million glial cells), its complexity and the similarity of neurotransmitters with the central nervous system (CNS).

One mechanism whereby the gut microbiome can contribute to neurologic disorders is via these neurotransmitters.  For instance, some “bad” gut flora lead to low levels of amino valeric acid and taurine, both of which are essential to making to making the neurotransmitter called GABA.  Patients with OCD and autism have low levels of GABA. 

On the other side of the equation, proper brain signaling to the ENS is important for producing a protein essential to a healthy intact epithelial barrier in the intestines: GDNF (glial derived neurotrophic factor).  Reduced barrier function is one of the main flaws that causes inflammatory bowel disease.  So, if the patient is suffering from stress, the brain in turn sends “distress” signals to the gut with the resultant worsening symptoms. 

Germ free mice have been the surrogate for humans in researching modifications in gut flora.  Since these specialized mice are germ sterile, researchers can establish any gut flora desired and measure its outcome.  These experiments are remarkable in that by establishing a “bad” flora researchers can make young, playful and social mice become withdrawn, and “depressed” and can also create mice who exhibit Parkinsonian movements and mice who suffer memory loss.

As exciting as this research is there are as yet no proven clinical applications for humans. 

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