Leaky Gut Syndrome. What is It, and How to Manage It?

Hi everyone! Today, we’re diving into a topic that’s been getting a lot of attention on social media and in wellness communities—leaky gut syndrome. While it’s not a formally recognized medical diagnosis, many people are curious about its potential link to digestive health and overall well-being. Let’s explore what the current science says about intestinal permeability, gut health, and how these factors might affect our bodies. We will look at the mechanism, the causes, and the management approach for leaky gut syndrome.

Leaky gut syndrome is not a medical diagnosis. But, there are situations where the epithelial barrier of the intestine becomes permeable leading to various diseases which can be called leaky gut syndrome. I will explain this in just a moment. Afterwards we will look at some of the causes of leaky gut and various drugs and lifestyle choices that can help.

Let’s start with understanding the epithelial barrier.

Intestinal cells lining the gut are called epithelial cells. Actually, cells facing any surface of the body are called epithelial cells. These intestinal epithelial cells are tightly joined together to create a barrier called intestinal epithelial barrier (IEB). This barrier prevents intestinal content from leaking into the intestinal wall or our body.

There are a variety of proteins that help bind these cells together. These proteins form structures called tight junctions. Some proteins involved in making tight junctions are occludin, claudins, and zonula occludens.

A look at the tight junctions

In this diagram you can see some of the tight junction proteins making these junctions.

Note that this barrier is not constantly closed or open. Cellular state and outside influences can alter the state of permeability based on the body’s need for essential molecules and restriction of harmful substances.

An imbalance in these regulatory influences can lead to compromised barrier integrity. When the epithelial barrier is compromised various microscopic and macromolecules present in the intestine can enter the gut tissue and even in circulation causing various pathologies and diseases generally called leaky gut syndrome. Again, not a medical diagnosis.

Now the question is how does the intestinal barrier become compromised?

A number of molecules and bacteria can damage the intestinal barrier. Some examples are molecules released from the active immune cells, gut microbiota, dietary components, and active immune cells. An imbalance of these factors can lead to tight junction protein damage leading to a compromised barrier.

Here is a more exhaustive list of factors that can compromise this barrier:

• Environmental stress
• Pathogens
• Genetic susceptibility
• Western diet
• Altered microbiota
• Drugs/antibiotics
• Immune response

That was how the barrier integrity is compromised, now let’s look at what happens when this intestinal barrier is compromised?

In a recent study from China the researchers note that a gram negative bacteria Prevotella can release lipopolysaccharides that can cross into the blood if there is a state of reduced epithelial barrier integrity for example due to inflammation. These LPS enter the brain and activate glial cells. Glial cells by the way are the immune cells of the brain. These activated glial cells cause brain tissue injury resulting in increased risk of Alzheimer’s disease. Interestingly the same LPS induces immune tolerance to inflammation in the gut leading to reduced risk of colorectal cancer.

To simplify, the researchers found that a bacteria in the intestine releases toxins that can pass through a compromised epithelial barrier and reach all the way to the brain leading to brain tissue damage.

For some more examples, damage to the epithelial cells and junctions can lead to:

• Inflammatory disease like
• Ulcerative colitis
• Crohn’s disease
• Coeliac disease

Metabolic endotoxemia leading to low grade inflammation and metabolic disorders like obesity and diabetes.

Leakage of metabolic endotoxins can also give rise to systemic diseases as mentioned earlier for Alzheimer’s disease.

Finally we want to know what we can do to avoid a compromised barrier? Of course identifying the actual cause and removing that cause is the primary approach, however, here is a list of drugs and lifestyle choices that can help. Make sure to talk with your doctor before using any of these methods. Also note that this is not an exhaustive list, however, it gets you looking in the right direction:

• Metformin
• Butyrate
• Berberine
• Drugs to reduce intestinal inflammation including aspirin. Note aspirin can result in increased bleeding risk.
• Intestinal flora regulation
• Probiotic supplements
• Microbiota transplant
• Lifestyle interventions
• Exercise
• Diet composition
• Metabolic surgery
• Intermittent fasting and controlling the dietary rhythm
• Diet rich in polyphenols, fiber, vitamins, and energy restricted diets.

That was the leaky gut syndrome. It is not an actual medical diagnosis but a condition of compromised gut barrier that leads to harmful substances to leak in our body and cause inflammation and disease. This situation can be avoided or managed by proper care as discussed.

References

DrBeen: Online Personalized Medical Education – DrBeen
https://www.drbeen.com/

Leaky Gut Syndrome: Symptoms, Diet, Tests & Treatment
https://my.clevelandclinic.org/health/diseases/22724-leaky-gut-syndrome

What is leaky gut syndrome? – Harvard Health
https://www.health.harvard.edu/diseases-and-conditions/what-is-leaky-gut-syndrome#:~:text=There%20are%20many%20reasons%20for,possible%20contributor%20to%20your%20symptoms.

Leaky gut: What is it, and what does it mean for you? – Harvard Health
https://www.health.harvard.edu/blog/leaky-gut-what-is-it-and-what-does-it-mean-for-you-2017092212451

Frontiers | Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.718356/full

fnut-08-718356-g001.jpg (957×610)
https://www.frontiersin.org/files/Articles/718356/fnut-08-718356-HTML-r1/image_m/fnut-08-718356-g001.jpg

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis | Geriatrics | JAMA Network Open | JAMA Network
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772918

Inhibition of colorectal cancer in Alzheimer’s disease is mediated by gut microbiota via induction of inflammatory tolerance | PNAS
https://www.pnas.org/doi/10.1073/pnas.2314337121

Enhancing intestinal barrier efficiency: A novel metabolic diseases therapy – PMC
https://pmc.ncbi.nlm.nih.gov/articles/PMC10018175/#:~:text=4.1.&text=Currently%2C%20treatments%20for%20intestinal%20barrier,metabolic%20diseases%20(Table%201).

Mechanisms regulating intestinal barrier integrity and its pathological implications | Experimental & Molecular Medicine
https://www.nature.com/articles/s12276-018-0126-x

Inhibition of colorectal cancer in Alzheimer’s disease is mediated by gut microbiota via induction of inflammatory tolerance
https://www.pnas.org/doi/10.1073/pnas.2314337121