Leaky gut, as crude as it may sound, is a breach of the intestinal lining. This leak may lead to the development of an alarming number of chronic diseases.
Also called Intestinal permeability, Leaky gut is becoming more prevalent in developed societies. The interaction that we have with our environment might be to blame. Novel foods and their ingredients, stress, drugs and medications, all lay waste to the structure and function of our intestines. That is unless we are smart about it.
The integrity of the gut barrier is of paramount importance. It serves to deny the access of harmful substances such as pathogenic bacteria, toxins, viruses and infections.
You can imagine the digestive system to be the first interaction our bodies have with the outside world. It is the gateway which exogenous substances gain access to our internal environment. A breach in this barrier has been associated with the following health conditions:
- Chronic Depression
- Irritable Bowel Syndrome
- Chron’s Disease
- Ulcerative Colitis
- Auto-Immune Disease
- Chronic Fatigue Syndrome, 2
- Chronic Liver Disease, Alcoholic Cirrhosis
- Rheumatoid Arthritis
- Type 1 & 2 Diabetes
Anyone with a leaky gut can attest to common symptoms. Those include fatigue, cognitive impairment, mood dysregulation, nutrient deficiencies, food intolerances, systemic inflammation and digestive complications. These symptoms are warning signals of an imbalance in need of attention. Much like that annoying red flashing light on the dashboard of your car; we are being prompted to ‘check engine’.
Hippocrates, the Mac Daddy of medicine was really onto something when he suggested that:
“All disease begins in the gut”
Thats some old school wisdom that is starting to become very apparent some couple thousand years later.
Taking this wisdom into consideration, it might be time we find ways to repair and preserve the intestinal wall.
There are already many foods, ingredients, herbs and spices which influence intestinal permeability. The question is, does Cannabis play a role in any way? If so, to what extent can cannabis have an influence?
What Happens When Your Gut Is Leaky?
On the surface of your intestines lie tiny hairs called villi. The Villi are what gives your intestines their enormous surface area for absorption. The Villi are composed of a lining of cells, only 1 cell thick. Just this is what separates the outside world with your internal environment.
Although your intestines are technically inside you, they are part of a canal which runs from your mouth right down to your butt. Called the Alimentary canal, this is considered a part of the outside world.
Enterocytes are what we called the cells of the villi. These allow passage to nutrients, and deny entry to pathogens such as bacteria and infections. The barrier of Enterocytes is permeable. The degree to which it is permeable, is influenced by a series of interactions.
Between each Enterocyte lies a gap called a tight juncture. This juncture can open and close acting much like a door from the intestinal tract into the bloodstream. The opening and closing action of this door is influenced by several factors:
- Psychological Stress
- Physiological Stress (exercise)
- Bacterial communication (microbiome)
Your Microbiome actually plays a leading role in the opening/closing of the tight junctures. It acts a gatekeeper – an intestinal bouncer who screens ingested particles and either permits or denies their entry.
The Microbiome is highly sensitive and highly intelligent. It regulates the opening and closing of the intestinal door via products that its bacteria secrete.
Your Microbiome houses all kinds of bacteria, which when taken together operate harmoniously. However, when it becomes depleted in diversity and density, that bad news. When imbalanced, it becomes overgrown with pathogenic microorganisms that take charge. These guys produce an Endotoxin known as Lipopolysaccharide (LPS) within their cell walls. This is especially true when Gram Negative bacteria dominate and beneficial bacteria are scarce.
The LPS that Gram Negative Bacteria secrete cues the opening of the tight junctures between the Enterocytes. LPS binds to receptors TLR-4 and CD14 on the surface of enterocytes. This engages membrane proteins which open and close the tight junctures. Illustrated in section A of figure 2.
Figure 1 – A normal Bowel compared to an inflamed, damaged bowel in Irritable Bowel Disease. You may notice the gaps between enterocytes, damaged enterocytes, and a depleted bacterial environment. On the right, you can also see how membrane proteins control the opening/closing of the tight junctures.
Additionally, LPS causes damage to the Enterocytes through inflammation. Not ideal as this further increases the distance of the tight junctures. The binding of LPS triggers the release of Pro-Inflammatory Cytokines TNF-alpha, IL-1beta, IL-6. Inflammation of the gut wall causes it to take on damage, reducing its structural integrity.
Damage to the structure and function of the intestinal wall opens up the tight junctures, which exposes our internal environment to invaders. Pathogens such as LPS and other antigens are now granted access into the bloodstream.
The gut wall is much like passport control at the airport, and the Enterocytes the booths which allow passengers to pass through. When passport officers occupy the booths, people get checked to ensure they are who they claim to be. They pose no potential threat.
With damaged enteroctyes, picture a few vacant booths. Say some passport officers are on a break. This leaves a few booths open to suspect individuals to sneak through.
Once suspect individuals sneak through passport control, they go on to board a flight. Imagine that a suspect boarding a flight is like a pathogen hitching a ride in the bloodstream.
The flight will provide transport to other countries, which you can think of as various organs in the body. These suspects can go on to conduct acts of terror in other countries. This is much like the Inflammation induced by LPS and other antigens on organs in the body.
In the development of Autoimmune disease this is what happens. Subsequently causing a confused immune system to attack healthy tissues and organs in the body in an attempt to deal with invaders. All this from a Leaky Gut.
How Can Cannabis Help?
Tight juncture regulation
Interestingly, our innate Cannabinoids – the Endocannabinoids, play an internal role in intestinal permeability via action on the CB1 receptors. Their action can both increase and decrease intestinal permeability.
It has been suggested that an overproduction of Endocannabinoids can lead to pathological changes in intestinal permeability. It is also suggested that an Endocannabinoid deficiency has underpinnings in Irritable Bowel Syndrome. IBS is a condition which is also underpinned by intestinal permeability. Regardless of over/underproduction of Endocannabinoids, it is clear that their action results in changes in gut barrier function.
Figure 2 – Illustrates the role of CB1 receptors in intestinal permeability, the action of Endocannabinoids (2-AG) in barrier function, and gut bacteria – LPS – CB1 receptor interactions.
Not surprisingly, Cannabinoids THC and CBD interact with the same Cannabinoid receptors in the gut. These engage membrane proteins, which alters intestinal permeability. Specifically, THC and CBD were found to increase the expression of the membrane protein Zonula occludens-1 ZO-1, decreasing gut permeability. This effect was a result of CB1 Receptor antagonism.
It is possible that CBD was responsible for this effect as it is a partial CB receptor antagonist. An antagonist suppresses action of receptor. Whereas THC is a partial agonist – activates action of receptor.
This is good news because decreases in intestinal permeability help to patch the holes in a leaky gut. Through regulating tight juncture function, cannabinoids may help prevent food particles, infections, and other inflammatory products from entering the bloodstream. This means that inflammation can be reduced, preventing further damage to the gut wall.
Chronic inflammation in the gut progressively damages Enterocyctes, which exposes gaps in the gut wall. This is how increases in intestinal permeability occur. Cannabis is a well known anti-inflammatory, arguably one of its most well known properties.
An exciting study found Cannabinoids THC and CBD to be effective in reversing disordered intestinal permeability induced by inflammation. Specifically, the inhibition of inflammatory cytokines IFNγ and TNFα by THC and CBD protected against gut wall damage, sparing permeability. The anti-inflammatory effect by THC and CBD occurred through action on the CB1 receptor.
Interestingly, another study showed a reduction in LPS induced inflammation via CB2 receptor activation in mice. This finding was also demonstrated in LPS induced pulmonary inflammation in mice. In the later study, the reduction in inflammation was in part due to CB2 receptor activation via THC, which effectively reduced levels of TNFα.
These findings suggest that LPS induced inflammation (endotoxin released from gram negative bacteria) could be addressed with the therapeutic action of THC.
Cannabinoids and other plant constituents of Cannabis have shown promise as antibacterial agents. This is especially important because antibacterial herbs can influence the composition of the microbiome.
The health of this microbial community is the first thing to slip, laying the grounds for a leaky gut. Since plant constituents of Cannabis have demonstrated antimicrobial activity, further study is needed. Of particular interest is their role in restoring the balance within the microbiome.
In someone with a leaky gut, you would typically find depleted levels of beneficial bacteria. This includes strains such as Lactobaccilus Acidophilus and Bifidobacterium bifidum. You would also find an overgrowth of Pathogenic Yeasts, Opportunistic Bacteria and pathogenic Bacteria.
This imbalance in a compromised microbiome leaves the gut wall exposed. Beneficial Bacteria are integral to protecting the integrity of the gut wall. They do this through modulating inflammation. Conversely, Yeasts such as C. albicans produce inflammatory metabolites damaging the gut wall. Its the same case for Gram Negative bacteria and their Inflammatory products – Lipopolysaccharide. When overgrown, these bacteria and yeasts can cause damage to the gut causing it to leak.
Therefore it is of interest to address the overgrowth of these micro-organisms with antimicrobial agents. Such agents include Cannabinoids and other plant constituents from Cannabis. These could assist in sparing the integrity of the gut wall.
A study investifgated the antimicrobial activity of essential oils made from Hemp. One particular preparation of Hemp oil, Futura, was capable of inhibiting the growth of all Gram + and Gram – Bacteria tested in addition to partially controlling yeasts. The beneficial action of the essential oil preparation was a combined action of Cannabinoids, Terpenoids, Flavinoids and Cannabinoid precursors.
Another study found similar results. Polyphenols extracted with alcohol from Hemp were found to exert potent antimicrobial activity on S. aureus (Gram +ve), P. aeruginosa (Gram -Ve), and C. albicans (yeast).
In light of the combined action of plant constituents of Cannabis on microorganisms; It may be effective to use cannabis as a whole plant extract.
Read more about Cannabis:
- Cannabinoids can effectively reduce inflammation in the gut, sparing the health of Enterocytes.
- Combined plant constituents of Cannabis can exert antimicrobial properties within the gut microbiome.
- THC and CBD can regulate intestinal permeability as analogues to Endocannabinoids.
- A whole plant extract, as an oil could be an effective means of administration for leaky gut.