This is such an important question in today's world.
Just watch a commercial (take a break from Netflix) and it's likely a pitch for autoimmune medications.
At the heart of autoimmune is our gut barrier (among others).
It's broader than the typical suspects you may think are autoimmune though:
- Dementia and Alzheimers are now showing connections there
- Anxiety and Depression
- Arterisclerosis and heart disease
- Diabetes and obesity
There are inflammatory processes there and the gut barrier is critical to chronic inflammation.
We'll get into all of it but more importantly, we'll look at substances like CBD and their effect on protecting and repairing the gut barrier.
There are powerful tools with very strong safety profiles which most people don't know about.
Just wait till you see the effects on IBS (Irritable Bowel Syndrome), a hallmark gut barrier disease.
We'll cover these topics:
- A quick introduction the gut barrier
- Gut barrier and autoimmune diseases
- Can CBD help with leaky gut syndrome
- Can CBD help with c Diff
- CBD and probiotics
- Other tools for gut barrier repair
- CBD dosage for leaky gut
- What's the best CBD for leaky gut
Let's get started. Before lunch, please.
A quick introduction to the gut barrier
It's the most under-appreciated organ in the body.
Yes, the brain is important but the gut barrier is literally the largest surface in contact with the outside world.
It must somehow determine friend (food) versus foe in an ever-changing world.
Bacteria. Viruses. Mold. Protozoa. Likely things we haven't categorized yet.
Throw on top of that all the new chemicals, fake sugars, fake fats, and medications that our gut must decide what to do with.
We did a huge review of omega 6 versus omega 3 fats. Huge player!
Look...it's the last defense from some very hostile forces that want to invade us!
There are three basic layers to this barrier from the outside world.
- The gut bacteria that both form a film and make up a barrier themselves
- The immune system guards which look for hostile invaders
- The actual physical lining of the gut which is make of interfitting blocks like paver stones
The three entities work in lockstep to let nutrients through but keep bad actors out.
At least...when it's working correctly.
What happens when there's a break in the defensive chain?
Let's go there now.
Gut barrier and autoimmune diseases
When our barrier becomes dysfunctional due to a weakness at one or more of the above links, bacteria and other players are able to slip through into our blood stream.
Scientist call the measure of their levels as serum LPS.
LPS is just a protein signature of bacteria. Serum means, in our blood.
Not to worry...our body's immune system is on the look out for these entities throughout and should find them, rally the troops, and eliminate them.
Here's the issue...this whole process of immune response is inflammatory.
The immune actors call in a host of weapons but there's always collateral damage.
Think of an infected cut.
It's red, inflamed, and painful.
That's our immune's response to the bacteria we're literally covered in.
It's estimated that bacteria on and in us outnumber our cells by 10,000 to 1.
Don't fret...it's always been that way and being too clean (especially during our youth) can actually lead to allergies and autoimmune.
Here's the issue.
If we have a chronic gap in our gut barrier, there is constant inflammatory response.
The immune system is not made for this "never ending war".
Let's take one example.
New research is showing that the genetic make-up of plaques in the arteries do not have the signature of our liver or things we eat (meat, cholesterol, etc).
They actually have the genetic profile of bacteria!!
Mouth bacteria specifically (another barrier).
"Most of the bacteria associated with plaques are also associated with the skin or oral cavity," Davies said. "Some are also commonly associated with the gastrointestinal tract."
This explains the seemingly odd tie between gum health and heart health.
The immune system detects stray bacteria and with an inflammatory response (very important), locks them away into the arteries.
It's a form of scarring just like when the immune system repairs a cut on your skin.
That's the hardening of the arteries effect which can lead to heart attacks.
Diabetes type 1 is a classic autoimmune disease.
New research is pointing to leaky gut issues as a corresponding contributor.
Which comes first?
First, studies utilizing human subjects affected by T1D or T1D-prone animal models have indicated that impaired intestinal barrier function occurs before disease onset.
Then there's zonulin, a Star Trek character.
Seriously though...zonulin is a chemical who's role is to maintain the "tight junctions" between those "pavers" of our gut barrier.
Too much of its activity and the junctions loosen up.
Reversion of intestinal barrier dysbiosis by adding a zonulin inhibitor ameliorated T1D manifestations in disease-prone rats.
They blocked zonulin and type 1 diabetes calmed down.
Scientist can actually induce diabetes with a substance called streptozocin which boosts zonulin.
When they dig down deeper into how this occured, escaping bacteria (to the pancreas in this case) were involved:
Additionally, STZ-injected wild-type (WT) diabetic mice displayed an altered gut microbiota compared with vehicle-injected WT mice, together with the translocation of bacteria to the PLNs.
Why so complicated? Basically, the gut bacteria had issues and bacteria were able to jump the barrier and end up in the pancreas.
When they gave antibiotics, this effect was blocked (as was the type 1 Diabetes progression).
Diabetes 1 is about as autoimmune as you get!
The gut barrier and gut bacteria are front in center.
We can literally take almost any autoimmune disease (which is starting to encompass a wide range of diseases) and find research on connections with gut barrier and microbiome.
Pick an off-one. Schizophrenia. How could gut barrier possibly play there?
What happens when these stray bacteria or other invaders cross into the brain and nervous system?
For example, immune activation related to gut-derived bacterial lipopolysaccharides (LPS) or various food antigens and exorphins were reported in major depression, schizophrenia, bipolar disorder, alcoholism and autism.
The gut actually acts as an inflammation early scout or thermometer for the rest of the body and the brain directly via the vagus nerve.
That's a fascinating read but we need to move on.
Let's first tackle CBD and then we'll look at some other powerful responders for gut barrier repair.
Can CBD help with leaky gut syndrome
First, CBD supports a key system in our body called the endocannabinoid system.
It's tasked with balancing other key systems:
- Nervous system - neurotransmitters like sertonin, GABA, and others
- Endocrine system - hormones
- Immune system - microglia and inflammatory response
Did you catch the last one!
That's the heart of autoimmune!
Let's jump right into CBD.
What about the gut barrier specifically?
Researchers looked at the damage of a particularly toxic bacteria called Clostridium difficile known to wreak havoc on gut barrier.
C. diff is the rap name.
What was CBD's effect following C diff damage?
Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.
We'll dive into c Diff further below.
It's not just bacteria though.
Many medications harm the gut barrier as well.
Front in center (in terms of sheer volume) are NSAID's.
The Advils, Motrins, etc of the world.
Millions of Americans use these daily for pain.
The effect on the gut?
In addition to gastric damage, NSAIDs are toxic to the intestinal epithelium, causing erosions, perforations, and longitudinal ulcers in the gut.
Millions of Americans.
It's like a gateway drug to autommune.
Researchers found that there may be a way to protect the gut barrier by boosting the endocannabinoid system.
Here's the net takaway:
Dual inhibition of FAAH and cyclooxygenase enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal inflammation.
That's a mouthful. Let's translate.
FAAH breaks down our biggest endocannabinoid, Anandamide.
Anandamide is called our "bliss" molecule and named after Anand, the goddess of bliss.
We'll let you guess how it feels in the body (THC mimics its effect along with side effects - see CBD versus THC here).
It's everywhere though and even in the gut.
That other chemical, cyclooxegenase is COX as in COX inhibitor as in Celebrex, Tylenol, and that class of pain relievers.
So...to button it all up...if we can block FAAH and COX, we can protect against the damage of NSAID's to the gut.
What can do this?
CBD does not activate CB1 and CB2 receptors (or even antagonizes them), but inhibits or activates several enzymes, transporters or receptors, including FAAH (inhibitor)
We have a huge review on research showing CBD directly protects the gut from NSAIDS.
One of CBD's most powerful levers is to bring down FAAH activity (see FAAH and the woman who can't feel pain, anxiety, or depression).
And as for all the inflammation in the gut associated with gut barrier issues:
CBD possessed potent anti-inflammatory action in DNBS-, TNBS and LPS-induced intestinal inflammation in mice and rats.
There's that LPS again….bacteria signature.
As for COX, check out CBD and Tylenol here but the effects of CBD on three markers of pain including COX:
All three markers, which were elevated by carrageenan treatment, were reduced in a dose-dependent fashion by CBD when compared to vehicle treated controls.
Research is here.
This isn't surprising as CBD has powerful antiinflammatory effects.
Let's cut to the chase.
CBD and gut permeability as it's called (basically...leaky gut):
Δ(9) -Tetrahydrocannabinol (THC) and cannabidiol accelerated the recovery from cytokine-induced increased permeability; an effect sensitive to CB(1) receptor antagonism.
That first one is THC and there are drawbacks there (see why you must use CBD to protect from THC here).
CBD doesn't have these drawbacks (tolerance, risk of addiction, psychoactive, etc).
To decipher the above results:
CBD helped the gut to recover from our immune system's overactive response (cytokines).
As for the various inflammatory "diseases" of the gut from IBS, Colitis, to Diverticulitus...CBD is showing impressive results.
It has been shown that cannabidiol (CBD), a cannabinoid with very low affinity for CB1 and CB2, has protective effects in murine colitis as observed by a reduction of colon injury, inducible nitric oxide synthase expression, reactive oxygen species production, MPO activity, and tumor necrosis factor alpha (TNF-α) level.
We have a full review on CBD and IBD or IBS.
The above is grab-bag of disease pathways in the gut.
What about CBD and gut bacteria, the third rail if you will?
This was important enough that we wrote an entire article on CBD and probiotics for our anxiety review.
This study is only beginning.
The microbiome isn't even a household word yet even though it functions almost as a separate organ touching every behavior you consider yours.
As for the gut barrier and CBD, let's look at rimonabant, the synthetic CBD:
Treatment with rimonabant for 12 days in obese ob/ob mice with gut barrier disruption and resulting metabolic endotoxemia (i.e., chronic increases in circulating LPS78) were met with reduced levels of plasma LPS and changes in the localization of the tight junction proteins, occludin and zonula occludens-1.
Let's translate this.
They gave this synthetic CBD to mice genetically bred to be obese who had gut barriers issues and high levels of bacteria in their blood.
After the fake CBD, bacteria blood levels came down and the the proteins that tighten up our gut barriers increased.
When looking at encephalitis, a nasty autoimmune disease of the brain (remember, bacteria can travel anywhere if the guards are asleep or injured), researchers pointed to the positive effect of CBD to changes in the gut bacteria:
Fecal Material Transfer (FMT) experiments confirmed that THC + CBD-mediated changes in the microbiome play a critical role in attenuating EAE.
EAE is encepthalitis. Attenuate...fancy way to say lessened.
Remember...most of the damage that results from our gut barrier permeability is the immune's system's response to stray bacteria...not the bacteria themselves.
It's overkill essentially.
Look at CBD's effect on this immune response:
CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B.
That's a mouthful but basically, CBD calmed the excessive immune response to bacteria in patients with ulcerative colitis.
Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.
Goodness. How many people are suffering or taking medications with nasty side effects for dozens of different GI and autoimmune diseases.
We compared Aricept at $500 versus fisetin (approx $10) for dementia at our Fisetin review.
Don't get us started on Humira and the host of auto-immune medications.
Let's look at some specific questions that pop up around gut barrier and CBD.
Can CBD help with c Diff
We mentioned c Diff up above since a study on CBD looked directly at this very dangerous bacteria.
This is a major player in the GI inflammatory disease pathway:
C. difficile produces two toxins, TcdA and TcdB, which damage intestinal cells and cause inflammation in the gut.
Antibiotics are a known trigger for c Diff issues. Too bad antibiotics have been used in most of our meat supplies as they "fatten" up the animals very quickly.
Turns out, they do the same thing for us!
The proton pump inhibitors for stomach acid may also pose a risk.
You know...Prilosec. Nexium. Prevacid and others.
Per the FDA:
Most studies found that the risk of C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among patients with PPI exposure compared to those without PPI exposure.
So...we're trading stomach gas for gut infection.
About half a million people are infected every year and the numbers are growing as is the severity.
It's the toxins that c Diff throws out which causes the damage:
Clostridium difficile fecal toxin level is associated with disease severity and prognosis.
These toxins destroy the lining of the gut, friendly gut bacteria, and more.
Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively.
Caco-2 cells are those that line the gut.
They die at a significant clip under the weight of c Diff toxin exposure.
As a result, the proteins (occludens and occludin) responsible for keeping the gut barrier intact are affected.
That's where the big study on CBD came in.
All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.
This goes to the damage of c Diff. We still have to eliminated it.
This can be helped by crowding it out with good bacteria.
The microbiome is in a constant state of flux...from meal to meal even!
Research probiotics for c Diff.
Expect some GI issues as there's usually turbulence when one species explodes in numbers or another one dies off.
Of course, work with your naturopath and/or doctor.
CBD and probiotics for leaky gut
As we mentioned, we wrote an entire article on CBD and probiotics for anxiety.
What about for gut barrier support?
Probiotics are just beneficial bacteria living in our gut.
They carry out vital (some essential) processes for us to live and thrive.
They also crowd out other bad bacteria such as c Diff above.
It's a total turf war down there with a constant state of flux and rebalancing.
We've seen above how CBD's positive effects on GI issues and even autoimmune disease is pointing to interaction with the gut bacteria.
This is not just GI!
We're talking about brain, joints, heart...anywhere you have an immune response (which is everywhere).
Look at the brain alone:
Microbiota regulate 5-HT1A, BDNF and NMDA expression (Sampson et al., 2016), and experimental transplantation of the microbiome of Parkinson patients to mice was demonstrated to increase their motor deficits, supporting the finding of a pro-inflammatory dysbiosis (microbiome imbalance) in that disorder.
- 5HT - Serotonin, our master "feel alright" neurotransmitter (see CBD and serotonin)
- BDNF - our nerve and brain fertizer (see CBD and BDNF)
- NMDA - just a master regulator of learning and focus
The last part is fascinating.
They took gut bacteria from mice with Parkinson's, transplanted them to healthy mice and...they developed telltale signs of Parkinsons!
We could stop right there (and just apply this effect to almost every disease out there with a partial "environmental" cause).
The complex interaction between probiotics and the endocannabinoid system are only now being teased out.
These are early days on both fronts unfortunately and the systems are incredibly complicated!
But they are intimately connected.
Let's bring back Anandamide, our primary endocannabinoid:
In addition, treatment with probiotics induced changes in the expression of mRNA for biosynthetic and degradative enzymes of anandamide in white adipose tissue that were paired with decreases in adiposity, suggesting modifications to endocannabinoid-mediated adipogenesis.
Basically, when they added probiotics, more anandamide was made in fat cells and consequently, there was less fat creation!
Check our CBD and perimenopause weight to see how powerful this effect is.
We know that probiotics can directly govern metabolism and anandamide may figure into this.
CBD's effect on anandamide?
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.
Here's the exciting piece of the puzzle between CBD and probiotics:
Furthermore, CB2 levels correlate to Lactobacillus concentrations and negatively with potentially pathogenic Clostridium species.
The more CB2 (the primary receptor that CBD supports) activity, the more healthy probiotics (lactobacillus) and the less bad bacteria (Clostridium which c Diff belongs to).
That's a fascinating effect but most of the supplements were finding exert their effects partially through the gut microbiome (berberine, fisitin, turmeric, etc).
This IS CBD's wheel house:
CBD's action with the CB2 receptor is just one of several pathways by which CBD can affect neuroinflammation.
In fact, CB2 receptors are more prominent throughout the immune system and….gut!!!
One note...for histamine and allergy sufferers, look at bifido's over lactobacillus.
This brings us to our next section which may be worth its weight in gold for anyone with autoimmune or leaky gut.
Other tools for gut barrier repair
We focus on CBD research but along the way, if we come across other substances that really stand out, we'll do a deep dive.
If it helps people, it's worth the time!
Two things come up prominently for gut barrier support.
Berberine and gut barrier
Berberine is the lead candidate there with impressive results.
It boosts a powerful probiotic called Akkermensia Munipalia which directly supports the mucus lining (our first defense) of the gut barrier.
Read the Berberine review here but its effects in IBD (Irritable Bowel Disease) is quite amazing.
Next up Fisetin and Gut Barrier
Fisetin is an all around powerful anti-inflammatory.
This effect occurs in the gut as well.
In addition, there are effects across longevity and age-related diseases due to the core pathways they affect.
Very exciting if you're a human and one that's aging!
Some practical questions now.
CBD dosage for leaky gut
We don't have hard research on this yet.
The general starting dose is 25-30 mg to test how your body responds.
This is about one dropper at the 1000 mg bottle level.
We can look to inflammatory diseases of the bowel for clues.
The study on gut inflammation and CBD (colitis specifically) was 10 mg/kg of weight.
For a 150 pound person, that's about 600 mg which is higher.
The studies on neurogenesis peaked at 300 mg.
The public speaking and anxiety study was at 600 mg but that was a one-off dosage.
We expect the range will be somewhere between 50-150 mg for systemic inflammation including gut barrier support.
Make sure to work with your naturopath and understanding doctor with medications and other concerns of course.
There are some key concerns on the type of CBD to use for leaky gut.
What's the best CBD for leaky gut
First, do no harm.
We have to make sure that we have very clean CBD.
It should have the following baseline qualities:
- Organically grown in the USA at an FDA registered farm
- 3rd party tested (we test ours twice)
- CO2 extracted (the cleanest method)
- No heavy metals
- No pesticides
- No solvents
- No mold
- No bacteria
Again, since our whole family uses Indigo Naturals, we actually test twice.
That's only the start (though most brands won't meet those requirements).
Then there's the type of CBD for gut barrier support.
Everyone on the market is pushing full spectrum although there's no research.
The research is on CBD Isolate by itself.
Here's the big issue…
40-60% of the population has allergy or histamine issues
This goes up for women and as we get older.
Many people new to CBD are finding out that all that plant material is having the opposite effect to what we discussed.
Histamine related GI issues.
That's the reason we eventually found and focused on CBD isolate.
All our allergic reactions went away with Isolate!
Histamine is inflammatory in nature (think of allergic reaction to foreign entities).
It's intimately tied to the gut for this reason where we're swarmed with "foreign entities" that want to gain entry.
Researchers are starting to look at this connection with leaky gut:
Recent evidence suggesting that mast cells may play a central role in the pathogenesis of irritable bowel syndrome paves the way for agents targeting histamine receptors as a potential therapeutic option in clinical treatment.
Mast cells are where histamine is released.
Check out CBD and histamines here for more information.
We don't want to set off those triggers and increase an inflammatory response in the gut.
That's going the wrong direction.
Be well. Be informed. Feel better.
Always work with a doctor or naturopath with any supplement!
The information provided here is not intended to treat an illness or substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.