Leaky Gut Syndrome and Autoimmune Disease

There are many protective barriers existing on human bodies. For example, they can be found in:

• Gut^[17,24]
• Airways
• Skin
• Oral cavity
• Vagina
• Placenta, etc.

Here we will focus on the barrier existing in the gut. In a perfect digestion world, only small building blocks are all that would be absorbed into our bloodstream^[14] – but this is not what happens when you have leaky gut.

Bricks and Mortar Model

The total surface area of the gastrointestinal system is approximately 300 to 400 sq. m.  Only a single epithelial layer separates us from enormous amounts of antigens of both dietary and microbial origin.^[25]

All the cells that line our digestive system are held together by a brick and mortar system called the “tight junctions”.^[14,23] These tight junctions hold the cells close together (like a glue of sorts). In other words, the barrier in the gut is composed of:

• Bricks
• Which is made of intestinal cells
• Mortar
• Which consists of intercellular tight junctions
• Researchers at the University of Maryland School and Harvard Medical School recently identified a molecule called zonulin that can play a detrimental role in the "mortar" part.^[1,9]
• ^{Zonulin is a novel human protein analogue to the Vibrio cholerae derived Zonula occludens toxin}
• ^{Zonulin can induce tight junction disassembly and a subsequent increase in intestinal permeability in non-human primate intestinal epithelial.}
• ^{Zonulin expression was raised in intestinal tissues during the acute phase of coeliac disease, a clinical condition in which tight junctions are opened and permeability is increased.}

 (Source: [30])

Figure 1.  Prevention of gut-barrier dysfunction in arthritis ameliorates joint inflammation^[30]

Leaky Gut Syndrome

The lining of your intestines is a sensitive environment critical to your health. Sitting on top of this cell lining is a layer of mucus that is also an important part of the barrier.^[13] This barrier's job is to regulate everything that passes between your intestine and the rest of your body. Together with the immune cells located in your gut, the barrier helps control how your immune system reacts to anything foreign. When the barrier is weak or comprised, you have a condition called leaky gut symdrome.

Video 1.  Gut Dysbiosis - Starving Our Microbial Self (YouTube link)

Leaky Gut Syndrome and Autoimmune Disease^[2,9,10,12]

The latest research on leaky gut syndrome and autoimmune disease shows that almost everyone with an autoimmune disease has leaky gut syndrome.^[3,4]

Leaky gut allows anything that is inside your intestines to be "seen" by the immune system that is lying beneath your intestinal lining. When this exposure is chronic, meaning that it goes on and on for months, the immune reaction over time begins to malfunction, putting you at risk for an autoimmune disease.

This is what happens: When your intestinal barrier is weak or broken down, partially digested food or antigens from bacteria and yeast can seep into your body, bump into the lymphoid tissue and immune cells in your gut, and then also get into your bloodstream. Your immune cells react by making lots of T helper cells, which are directly in charge of revving up the killer cells and antibody-producing cells to attack anything they don't recognize as an invader. However, problems can occur when your body starts producing an abundance of T helper cells, especially if the T regulator cells don't do their job to turn this attack off.

Symptoms

People with leaky gut syndrome often have digestive symptoms such as constipation or gas and bloating after they eat. But it is also possible to have leaky gut syndrome and have absolutely no digestive symptoms at all. Instead you might feel your hands and feet swell up after you eat, your muscles are tight and stiff in the morning, and you have brain fog and difficulty thinking after eating certain foods. These symptoms are a result of what's called systemic inflammation,^[2,8] which simply means that there are irritating molecules running around your body after eat certain foods. Sometimes it is hard to know which food is the culprit because it seems like you react to so many.

Besides the conditions above, general symptoms of leaky gut are vast given the indirect impact of a leaky gut on the entire body’s health and capacity for handling stressors. Some of the most common include:^[5]

• Allergies and skin rashes
• Anxiety, fatigue, poor concentration, irritability, moodiness
• Headaches
• Impaired immune functions or frequent colds

What Causes Leaky Gut?

There are many things that can cause leaky gut. For example, the mortar in between the cells gets damaged by things like:^[2]

• Dysbiosis  by exposure to yeast candida, parasites, bad bacteria, or glyphosate (i.e., the active ingredient in Roundup)
• Bad bacteria can secrete enzymes that destroy the "mortar" between the cells
• In 2013, scientists show that gut dysbiosis, brought on by exposure to glyphosate, plays a crucial role in the development of celiac disease.^[20]
• Severe or chronic stress
• Acute emotional or physical trauma, such as surgery or food poisoning
• Alcoholism
• Certain medications
• Antibiotic use
• Non-steroidal anti-inflammatory drugs (NSAIDs), medications such as ibuprofen and other prescriptions.
• Viral infection
• Infections or exposures that were never resolved, such as traveler's diarrhea or a parasite
• Toxins
• Those secreted by the yeast candida:
• They can bind to part of the protective barrier, breaking it down
• They also can create pores across the membranes of the barrier
• Chemotherapy
• Vitamin D Deficiency
• Vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.^[23]

When leaky gut happens, you are also likely to develop food sensitivities. These food sensitivities can happen not only in childhood but later in life, too. It's true that some people can outgrow food allergies. However, symptoms of food allergies can return just as mysteriously as they disappeared.^[16] In [17], scientists have speculated on the effect of increased intestinal permeability on the onset of sensitization towards dietary antigens. So, it seems that the recurring of food sensitivities could be related to the permeability of intestinal barrier.

Conclusions

Maintaining a strong barrier is the best way to keep your immune system healthy, which means that it knows when to turn on and off, knows the difference between self and not self and has tolerance of the good bacteria lining the digestive tract.

Photo Credit

• Arthur John Elsley
• Figure 1 in [20]

References

1. A. Fasano. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol 2012 Feb; 42(1):71-78.
2. The Immune System Recovery Plan by Susan Blum, M.D. M.P.H.
3. Linda Chia-Hui Yu et al. Host-microbial interactions and regulation of intestinal epithelial barrier function: from physiology to pathology. World J Gastrointest Pathophysiol 2012 Feb 15; 3(1):27-43.
4. Katherine R. Groschwitz and Simon P. Hogan. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 2009; 124:3-20.
5. Leaky Gut (Core One Health)
6. Fasano A, Not T., Wang W. et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355:1518–1519.
7. David Seaman: Inflammation From Our Diet Is Killing Us Slowly
8. Body mass index and musculoskeletal pain: is there a connection?
9. New Research Shows Poorly Understood “Leaky Gut Syndrome” Is Real, May Be the Cause of Several Diseases
• In the 1980s, the UCLA researchers found that leaky gut preceded inflammation, implying that the leakiness plays a key role in Crohn's disease development.
• Harvard celiac researcher, Alessio Fasano, MD found that our bodies make a protein (with the nifty name, “Zonulin”) that essentially unzips the tight junctions that seal the intestinal lining.
10. Researchers Find Increased Zonulin Levels Among Celiac Disease Patients
11. Dr. M's Seven-X Plan for Digestive Health: Acid Reflux, Ulcers, Hiatal Hernia, Probiotics, Leaky Gut, Gluten-free Gastroparesis, Constipation, Colitis, Irritable Bowel, Gas, Colon Cleanse/Detox & more
12. Ulcerative colitis flare-ups: 5 tips to manage them
• Ulcerative colitis, like its sister condition Crohn's disease, is treated as an autoimmune disease.
13. Mucus is Retained in Cystic Fibrosis Patients’ Cells, Leads to Potentially Deadly Infections
• This is what happens when your mucus malfunctions:
• Cystic fibrosis is that mucus lining the lungs, pancreas and other organs is too sticky, which makes it difficult for the organs to work properly and, in the lungs, attracts bacteria and viruses resulting in chronic infections.
14. Physiology Of The Small Intestine
15. Sarah Ballantyne on The Paleo Approach and the Autoimmune Protocol
• Leaky gut could be influencing the immune response
• Eating to promote intestinal health is the same as eating to support immune health
16. Can you outgrow your allergies?
17. Gut permeability and food allergies
18. The Epithelial Gatekeeper Against Food Allergy (good)
• Intestinal epithelial barriers play a crucial role in the maintenance of gut homeostasis by limiting penetration of luminal bacteria and dietary allergens, yet allowing antigen sampling via the follicle-associated epithelium for generation of tolerance.
19. Early Studies Linking Gut Bacteria to Atherosclerosis, Offer Tantalizing Glimpse at New Drug Target
20. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance (31 citations)
21. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota
22. Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease
23. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier
24. Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science. 2005 Mar 25;307(5717):1920-5.
• The Gut Epithelial Barrier – The primary cellular barrier of the bug in preventing antigens encountering the immune system is the single layer of gut epithelium
25. D M Saulnier, S Kolida, G R Gibson. Microbiology of the human intestinal tract and approaches for its dietary modulation. Curr Pharm Des. 2009;15(13):1403-14.
26. Broccoli improved digestive issues similar to symptoms of leaky gut and colitis in animals
• Same for other vegetables, like brussels sprouts and cauliflower 
27. Gut microbes could help trigger multiple sclerosis
28. Putting a stop to leaky gut (Harvard Medical School)
29. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics
30. Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease
31. Extra Virgin Olive Oil Reduces Gut Permeability and Metabolic Endotoxemia in Diabetic Patients
• Addition of Extra virgin olive oil to a Mediterranean diet or chocolate improves gut permeability and low-grade endotoxemia.