Leaky Gut and Leaky Brains…and Disease

If you remember, my last post was a quick update on what we currently know about the microbiome-depression link, and I mention leaky gut with a promise to write more about it this week.  Toward that end, on Friday evening, I read an article from the journal Microorganisms entitled, “Leaky Gut, Leaky Brain?,”[i] and was looking forward to sharing some highlights with you this week.  More on this in a moment.

A little coincidental tangent: on Saturday, I came across an article on Helio summarizing the “Psych Congress” summit about the microbiome.[ii]  This particular piece is about the gut-brain connection in psychiatric illness and I realized it fit in perfectly with today’s leaky gut focus while also being a great segue from talking about depression.  “We are not better today at treating depression than we were 70 years ago,” says the presenting doctor.  (Well, that is er…depressing.)  Depression, he goes on to state, is an inflammatory disease, pointing to those same raised blood markers I mention in my last post.  Simply prescribing the usual anti-depressants is simply not good enough for most people.   The microbiome needs to be addressed.

This doctor’s presentation included information about things you can do now:  an anti-inflammatory low-processed-sugar diet that includes fruit, veggies, whole grains, lean meat, fish, etc. I also liked his suggestions to “tidy up blood-brain barrier leakiness”:  curcumin, green tea, garlic and cinnamon, probiotics and prebiotics .

How’s that for timely?  And this, from a mainstream physician!  As it turns out, the  article I am covering today (“Leaky Gut, Leaky Brain?”), starts off with an extremely pertinent quote:  “’Leaky gut’ syndrome…has attracted much attention in recent years and for decades, was widely known in complementary/alternative medicine circles.” That is absolutely correct.  I remember only too well when the concept of a leaky gut was considered “alternative” and the gut-brain connection was scoffed at by mainstream medicine…and I’m not that old!  I keep telling you that times they are a’changing! (Thank goodness.  As I always say, just because something is unproven doesn’t mean it’s wrong.  And there is something called common sense…)

The blood-brain barrier is a membrane very similar to the epithelial lining of the gut.  Both are made up of tightly packed cells that, when healthy, prevent infiltration by  anything not meant to get through.  We know that inflammation in the gut causes those tight cell junctions to open up in the gut, allowing bacteria, bacterial toxins, undigested food, etc. directly into the blood stream causing immune havoc.  Why was it ever a reach to believe that those “invaders” could also cause inflammation in the blood-brain barrier causing central nervous system issues?  I really don’t understand why it has taken so long for this concept to become commonly accepted.

Anyway…this paper reviews what we know about “…the possible neurophysiological basis of leaky gut; leaky brain disease; and the microbiota’s contribution to inflammation, gastrointestinal, and blood-brain barrier integrity…”  It was actually pretty technical, so I’ll just stick to some of my favorite highlights.

1. The author points out that it is not only the gut and immune system that evolved in the presence of trillions of microorganisms and their byproducts – it is also the central nervous system: “…dysfunction is as likely to arise from the absence or disruption of normal microbial components as it is from their inappropriate distribution ratios.”  That is, both biome depletion and dysbiosis have negative consequences that reach far beyond just gut health.
2. In the case of dysbiosis, pathogens have developed mechanisms to target the host barrier integrity so that they can invade other organs and tissues. For example, the bacteria Neisseria meningitides is found in the nasal passages of about 10% of healthy people, but under certain circumstances, has the ability to disrupt the tight cells of the mucosal barrier of the nasal passages to make its way into the blood stream and the brain, causing meningitis.
3. Celiac, he states, is the “archetypal leaky syndrome” as the inflammation of the gut in the presence of gluten is well-known to lead to involvement of many other organs, including the brain. Symptoms can include not just GI symptoms but also issues with motor function, headaches, cognitive impairment and neuropsychiatric disease.
4. He points out that there is an emerging body of work that suggests that maternal microbiota directly affects blood-brain barrier development in utero, and thus, the developing brain in infants.
5. Another crucially important point: “Stress has immunologic consequences as well, and also has a role in these interactions.”   Stress is proinflammatory.
6. The commensal bacteria of the gut have been shown to preserve gut and brain barrier integrity. Germ-free rodents, for example, have increased permeability and this was improved when normal bacteria of the rodent biome were introduced.
7. Autism most certainly appears to be an illness of gut-brain barriers dysfunction. A post-mortem study comparing 8 people with autism versus 33 normally-developing people found distinct gut and brain barrier permeability in the autism group.  A second post-mortem study of 9 individuals with ASD versus 12 without showed that 75% of the ASD people had reduced components necessary for normal barrier forming and 66% had increased levels of molecules that lead to intestinal permeability problems. The same issues were found in people with schizophrenia.

A final quote to share with you.  I have added the bold highlights to emphasize to you just how far reaching are the consequences of blood-brain barrier dysfunction:

“A dysfunction of the blood brain barrier leading to a ‘leaky brain’ can be linked to various neurological diseases, including autistic spectrum disorders (ASD), dementia, Alzheimer’s disease, depression, and schizophrenia.  A breakdown in the blood brain barrier was observed in patients with major psychiatric illnesses.  Moreover, the blood-brain barrier may become ‘leaky’ in select neurological diseases that have an immunologic component, such as multiple sclerosis (MS), Alzheimer’s disease, brain trauma, edema, brain cancers, amyotrophic lateral sclerosis [ALS], meningitis, and systemic diseases such as liver failure.  Moreover, co-metabolism within the gut-brain-endocrine interactome play a role in the same neurodegenerative disorders, including Parkinson’s disease (PD)….”

So to sum it all up, it is starting to look like most chronic inflammatory diseases are caused by a dysfunction of the gut barrier. Treating biome dysbiosis and/or depletion may turn out to be the cure for more than we can possibly grasp right now.

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[i] Obrenovich, MEM. Leaky gut, leaky brain?  Microorganisms. 2018;6(107). doi: 10.3390/microorganisms6040107.

[ii] https://www.healio.com/psychiatry/practice-management/news/online/%7Bad397d11-3ba5-447d-98ec-edbc1a1c86a9%7D/microbiome-gut-brain-axis-plays-role-in-evaluating-treating-psychiatric-illness?page=2