Further evidence the gut may be involved in Parkinson’s disease

A number of studies have linked Parkinson’s disease with issues arising in the gut.  While we don’t know the direction of causality, if the gut changes the brain or vice versa, a small amount of evidence indicates that the changes may be initiated in the gut.

A study published yesterday indicates that one of the genetic mutations that predisposes people to Parkinson’s disease may be acting outside of the brain.  Mutations in the gene LRRK2 increase the risk for Parkinson’s, but aren’t sufficient to cause the disease on their own.  Instead, some environmental factor or factors must trigger the genes to cause the disease.

An inflammatory cascade from the gut?

One of the more interesting aspects of this study was how they triggered LRRK2 to create an environment that could lead to Parkinson’s.  The researchers injected the mice with our old friend lipopolysaccharide, a molecule you have in your gut in spades.  When the mice with LRRK2 mutations were injected with lipopolysaccharide, they experienced an inflammatory response 3-5x that of mice without the mutation.

Making matters worse, the inflammatory cytokines created outside of the brain managed to creep in to the brain and activated microglia.  This led to neuroinflammation and pathology consistent with Parkinson’s disease, as neurons in the substantia nigra were lost.

This data is actually interesting for another reason.  While LRRK2 mutations can lead to Parkinson’s disease, they only account for a small number of Parkinson’s cases.  This study provides a link between excessive inflammation in the body contributing to inflammation in the brain.

Lipopolysaccharide appears to be a primary contributor to chronic inflammation.  I’ve covered lipopolysaccharide a number of times.  First, I covered why it’s in your gut, and the negative consequences of it slipping from the gut in to the bloodstream.  Next, I covered how the feeding/fasting cycle and circadian rhythms play a role in lipopolysaccharide entering the bloodstream.

It’s not necessarily the gut…

It’s important to note that this piece of data isn’t gut specific, it simply indicates that the gut may possibly be involved.  LRRK2 may overreact to any form of infection and cause an excessive inflammatory response.  But since the study did show that lipopolysaccharide can cause excessive inflammation in mice with the LRRK2 mutations, people with these mutations should do anything in their power to prevent it from slipping in to the bloodstream.  In theory, this should reduce the risk of Parkinson’s disease.


We live in a time where access to your DNA is both cheap and accessible.  Armed with the information from this study, it would behoove you to make a concerted effort to prevent lipopolysaccharide from slipping past the gut in to your blood if you have one of the mutations in LRRK2 that increases your risk of Parkinson’s.  This would include optimizing circadian rhythms, reducing the number of meals you eat, reducing alcohol intake, and consuming adequate amounts of fiber every day(>35g/day).  Actually, that’s great practical advice for anyone.


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