Thursday, June 12, 2014

Stress and heart attack...Are gut bacteria involved?

There has been a long established link between stress and heart attack.  A new study published in the open access journal mBio may provide a key to why atherosclerotic plaques rupture due to stress, causing a heart attack.  The key to this process may reside nowhere near your heart, but about a foot lower in your gut.  The researchers found some unusual things in this study, so let's take a look piece by piece.

In the first part of the study, the researchers were looking for evidence of bacteria in arteries with plaque accumulation removed from 15 people with advanced atherosclerosis.  Prior to this study, there had never been evidence of bacteria within plaques found on blood vessel walls.  All 15 tested positive for bacterial genes indicating the presence of bacteria in these plaques.  The next step was to test for biofilms, a colony of multiple species of bacteria that adhere to surfaces and one another while providing a matrix that is impervious to the immune system and antibiotics.  They looked at 5 random samples and found that each contained between 10-18 different strains of bacteria that were confined within a matrix, indicating that they indeed had formed biofilms.  This is important because the researchers believe that activation of the stress response could cause these biofilms to breakdown and potentially cause a rupture, which was what they tested for next.

In 6 of the 15 samples, the bacteria Psuedomonas aeruginosa was found.  When biofilms of P. aeruginosa are exposed to free iron, they disperse and break apart, potentially due to the use of degrading enzymes by the bacteria.  When stressful events occur, they cause the release of norepinepherine which frees up iron bound to the protein transferrin.  The next step for the researchers was to determine whether P. aeruginosa biofilms dispersed under physiological conditions similar to what one would experience during activation of the stress response, which did indeed happen.  The researchers hypothesize that this could be happening due to degrading enzymes that may cause the plaque to weaken and break off, with the plaque finding it's way in to a narrower vessel and blocking it, causing a heart attack.  However, they also point out that other factors are likely involved.  This is all fine and dandy, but how is the gut involved?

P. aeruginosa is commonly found in the human digestive tract where it typically remains benign*.  Under certain environmental conditions, it can step out of the gut and in to the bloodstream where it typically takes up residence in blood vessel walls(1, 2).  The interesting part is the environmental conditions that cause it to leave the gut.  One method involves zonulin and the dissolution of tight junctions, aka leaky gut(2).  The second involves the presence of immune system activation, specifically the cytokine interferon-gamma.

When interferon gamma binds to a receptor on P. aeruginosa, it causes it to secrete a toxin that makes the gut more permeable and another that allows it to move across the intestinal lining and enter the bloodstream(3).  Both of these mechanisms are related to Celiac disease and Non-celiac gluten sensitivity in people with the genetic variant for Celiac disease.  In all people, gluten causes the release of zonulin which opens up the tight junctions and causes a leaky gut; in people with Celiac or gluten sensitivity, this response is exaggerated.  In both of these groups, interferon-gamma levels are high.  In people with celiac disease, it's always high; in people with NCGS that have the genetic variant for Celiac disease, interferon-gamma levels are high when gluten is consumed but normal under gluten free conditions(3).  Approximately 30% of Caucasians carry the variant that is associated with Celiac disease and an exaggerated interferon-gamma response.

All is not lost, however.  The composition of your gut flora can prevent P. aeruginosa from becoming a problem.  Butyrate, a short chain fatty acid produced by bacteria in your gut, helps prevent a leaky gut.  It also has antibacterial activity against P. aeruginosa, as do other short chain fatty acids produced by fermentation by our gut bacteria(4).  To promote butyrate and other short chain fatty acid levels in your gut, increase the amount of fiber and resistant starch from vegetables in your diet.  This can also improve overall colon health as butyrate also blocks interferon-gamma signaling there, which reduces inflammation in the gut.

More interesting than the potential mechanistic relationship between stress and heart attacks found in this study is that they found bacteria of multiple types in biofilms on blood vessel walls.  We are entering some very interesting times.  More and more health complications are associated with poor GI health, even ones with seemingly no relationship from a symptom perspective.  No one ever thought that past infections could accumulate in the way this study showed evidence for.  In my opinion, people are going to need to shift away from looking at their diet quantitatively(How many calories, carbs, etc.) and more qualitatively(Types of foods, specifically vegetables) if health is their goal.  In other words, calories in vs calories out needs to be buried.  With gut health seemingly related to so many health conditions and the food environment being optimal for gut health problems, I will not be the least bit surprised to see an uptick in many of the chronic diseases that we are currently dealing with.

*It's important to note that P. aeruginosa can also enter the blood via a lung infection and wounds.