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Article

Leaky Gut Syndrome

Friday, December 17th 2021 10:00am 13 min read
Dr. Jessica Peatross dr.jess.md @drjessmd

Hospitalist & top functional MD who gets to the root cause. Stealth infection & environmental toxicity keynote speaker.

Leaky gut syndrome, which is intestinal permeability, is becoming more common. It occurs when the lining of your intestines develops microscopic holes that allow toxins, microbes, and undigested food particles to pass through into your bloodstream. This may increase chronic inflammation, which in turn can result in a chronic immune response. This is a critical issue since leaky gut syndrome may cause chronic symptoms, histamine intolerance, autoimmunity, and other chronic health conditions.

Let’s take a deeper look at what leaky gut syndrome is, the symptoms, its link to histamine intolerance, and lab markers to help determine if you have a leaky gut.

What is leaky gut syndrome?

A healthy gut lining is naturally semi-permeable. It allows key micronutrients to pass through microscopic holes into your bloodstream. These holes are too small for toxins, microbes, or undigested food particles to pass through. This helps to keep your gut and the rest of your body healthy. Pathogens that can’t pass through will eventually get eliminated through urine or stool.

A leaky gut can develop when inflammatory foods, toxins, infections, chronic stress, or other harmful factors cause serious damage to the gut lining. They cause the tiny holes to grow bigger making your gut lining more permeable than it should be. The holes are big enough for undigested food particles, toxins, microbes, and pathogens to easily move through.

When this happens, it can cause serious damage, chronic inflammation, and a compromised immune system. It can lead to an ongoing chronic immune response to these foreign substances, which increases the risk of chronic symptoms, autoimmunity, and other health problems.

A growing number of scientific studies suggest that leaky gut is a major cause of many chronic health conditions. A 2021 study published in PLoS One has found that intestinal permeability may also increase the risk of metabolic health issues.

Symptoms of leaky gut syndrome

Signs and symptoms of leaky gut syndrome may include:

  • Autoimmune diseases, such as Celiac disease, Crohn’s disease, rheumatoid arthritis, Hashimoto’s thyroiditis, lupus, or psoriasis
  • Food allergies, food sensitivities, or food intolerances
  • Skin problems, including acne, rashes, eczema, or rosacea
  • Fatigue
  • Insomnia or other sleep issues
  • Fibromyalgia
  • Chronic fatigue syndrome
  • Digestive issues, including bloating, gas, constipation, diarrhea, nausea, or irritable bowel syndrome (IBS)
  • Brain fog, difficulties concentrating, memory troubles
  • Mood imbalances, including anxiety and depression
  • Headaches or migraines
  • Chronic muscle or joint pain
  • Getting sick often, slow recovery from illness, and other signs of poor immune health
  • Seasonal allergies or asthma
  • Hormonal imbalances, including irregular periods, PMS, or polycystic ovarian syndrome (PCOS)

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Leaky gut syndrome and histamine intolerance

Leaky gut syndrome can also increase your risk of developing histamine intolerance with symptoms including inflammation, bacterial overgrowth, and a deficit of the diamine oxidase (DAO) enzyme.

Your body produces histamine, which helps it get rid of allergens through an immune response. In addition, histamine helps support digestion by triggering the release of stomach acid and supports overall health by communicating with your brain.

Too much histamine can be problematic because your body won’t be able to break all of it down. Too much histamine means you have developed histamine intolerance, which can lead to digestive problems, skin issues, anxiety, migraines, and more. It may also contribute to chronic health issues.

A 2018 study published in Mediators of Inflammation and a 2013 study published in the British Journal of Pharmacology showed how histamine works in the modulation of the immune and inflammatory response in inflammation. If you have intestinal permeability, it means that foreign pathogens and larger food particles can pass into your bloodstream, which can impact histamine production.

Leaky gut and excess histamine

A gut microbiome imbalance (dysbiosis) is a common occurrence with leaky gut syndrome. It can increase the risk of bacterial overgrowth, which increases chronic inflammation and gut health issues. Some bacteria can increase histamine production like L. casei and L. Bulgaricus.

Leaky gut syndrome may also increase the risk of a deficiency in the diamine oxidase (DAO) enzyme. The DAO enzyme is an important enzyme that’s critical for the breakdown of excess histamine and keeping your histamine regulated correctly. Not having enough DAO enzymes means that your body won’t be able to deal with the excess histamine increasing the risk of histamine intolerance.

Symptoms of histamine intolerance may include:

  • Allergies or asthma attacks
  • Crawling sensation on skin or scalp
  • Vertigo
  • Tachycardia
  • Low blood pressure
  • Hypertension
  • Congestion or runny nose
  • Headaches or migraines
  • Diarrhea or constipation
  • Hives, eczema, rashes, psoriasis, and other skin problems
  • Flushing
  • Anxiety
  • Abnormal menstrual cycle or PMS

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Key lab markers for leaky gut syndrome and histamine

To determine if leaky gut syndrome is impacting your histamine levels, consider testing for these markers.

DAO

The DAO enzyme is a key enzyme that breaks down excess histamine and keeps your histamine levels regulated correctly. Not having enough DAO enzymes means that your body won’t be able to break down all the excess histamine, which may lead to histamine intolerance.

A 2016 study published in the International Journal of Immunopathology and Pharmacology found that people with histamine intolerance had lower levels of DAO enzymes. A 2018 study published in Allergy found that decreased DAO levels were associated with higher histamine levels and histamine intolerance. Healthy DAO plasma levels may range between 15 and 50 U/ml, however, during pregnancy, they may increase up to 500-fold.

Histamine

Histamine is a key player in fighting allergies, good digestion, and brain health. Too much histamine or histamine intolerance is problematic. Checking your histamine levels is important to detect histamine intolerance, which may be related to leaky gut syndrome as well.

A 2021 review published in Nutrients found that histamine intolerance is connected to low intestinal DAO enzyme levels. Normal histamine levels are between 0.3 and 1.0 ng/mL (23).

DAO/histamine ratio

The DAO/histamine ratio helps identify imbalances between histamine and DAO levels. Even if the DAO enzyme level is normal when histamine is high, symptoms can occur. A low ratio indicates that there may not be enough of the DAO enzyme relative to the amount of histamine in your body.

Zonulin

Zonulin is a protein that is synthesized in your intestinal and liver cells. It helps to modulate the permeability of the intestinal lining. A 2016 review found that zonulin plays a role in regulating the function and health of the intestinal barrier and can play a role in the development of chronic inflammatory diseases.

A 2020 review published in F1000 Research found the same results. Zonulin-mediated intestinal permeability can increase the risk of chronic inflammatory diseases, including autoimmune diseases, like metabolic disorders, obesity, gestational diabetes, hyperlipidemia, insulin resistance, non-alcoholic fatty liver disease, IBS, type 1 diabetes, multiple sclerosis, and ankylosing spondylitis. It may also play a role in certain cancers, environmental enteric dysfunction, and neuroinflammatory conditions like major depressive disorder, schizophrenia, autism spectrum disorder, and chronic fatigue syndrome.

The normal median concentration of fecal zonulin is around 61 ng/mL (+/- 46 ng/mL) making 15 to 107 ng/mL the normal range (14). Normal serum zonulin levels are a median of 34 ng/mL (+/= 14 ng/mL) making 20 to 48 ng/mL normal. High zonulin levels may indicate intestinal permeability, intestinal inflammation, and gut health issues.

Lipopolysaccharides (LPS)

Lipopolysaccharides (LPS) are a key part of the outer membrane of gram-negative bacteria. They are found in the outer layer of the membrane and are exposed to the surface of the cell. They help to support and stabilize membrane structure.

LPS can cause changes in the intestinal lining which may lead to the development of certain health conditions. High LPS levels can increase intestinal permeability and related gut issues, such as Crohn’s disease. Normal levels of LPS are very low at 5 picograms per mL blood or below.

Low elastase-1

Pancreatic Elastase 1 is a digestive enzyme secreted by your pancreas. Determining elastase 1 and fecal calprotectin levels can identify pancreatic issues and find a possible connection between pancreatic problems and intestinal inflammation.

Normal elastase-1 levels are below 200 mcg elastase/g. Low levels are linked with poor pancreatic function, gallstones, cystic fibrosis, and hypochlorhydria.

GI map test markers

The GI Map Stool Analysis helps identify dysbiotic flora, bacterial, parasitic, and viral pathogens, potential autoimmune triggers, and other intestinal health markers. It helps identify key health issues and pinpoint markers to check for leaky gut syndrome.

High steatocrit

The GI map also tests for steatocrit levels, which shows the amount of fat in feces. Fecal steatocrit levels are a good indication of intestinal health.

Normal steatocrit levels are between 0 and 14.9 percent. High levels of steatocrit indicate fat malabsorption, which may be due to intestinal issues. It is also a potential marker for low stomach acid, poor bile flow, reduced pancreatic lipase, and potentially poor liver health.

Abnormal sIgA

This test can tell a lot about mucosal health and immune health. Poor levels may indicate intestinal issues, IBS, IBDs, or food sensitivities as well. Normal sIgA levels are 5.2 +/- 0.94 ug/mL (28). Low fecal sIgA may indicate a suppressed gut immune system, chronic dysbiosis, antigen exposure, protein malnutrition, immunocompromised state, or chronic stress. High fecal sIgA may indicate acute infections, acute stress, food sensitivities, or chronic dysbiosis. High anti-gliadin IgA may indicate an immune response to gluten.

High calprotectin

The test checks for certain markers of inflammation. Calprotectin levels look for intestinal inflammation. Looking at elastase 1 and fecal calprotectin levels can help identify pancreatic issues and find a possible connection between pancreatic problems and intestinal inflammation. This test is very important for the diagnosis of irritable bowel disease.

Normal calprotectin levels are between 10 to 50 or 60 μg/mg (30). High levels may indicate inflammatory bowel disease and help us to differentiate from irritable bowel syndrome. Food allergens, polyps, infections, diverticulitis, and colorectal cancer may also cause high calprotectin levels.

Basic blood testing markers

Basic blood testing markers to consider include stomach acid, malabsorption, and other digestive issues. Stomach acid (HCL) is essential for digesting protein, absorbing key minerals such as calcium, iron, zinc, and phosphorus. It is also necessary for sterilizing food coming into our bodies and keeping the overall bacterial and microbial balance in order.

Stressors, some infections, and other health conditions may inhibit the ability to produce enough HCL. A classic pattern for low HCL as seen on functional blood analysis includes the following: Low total proteins (under 6.9), low BUN (under 13), low globulins (under 2.4) and high A/G Ratio (over 2.0), low chloride (under 100), high MCV (over 92).

Low total proteins

Eating too much or too little protein can affect stomach acidity. Total protein measures the total protein levels in your blood.

Serum proteins are separated into albumin and globulins, albumin being the one at the highest concentration. Too much or too little protein in your diet can often cause elevated or low levels of total protein. Uric acid and HCL levels can also affect your total protein count.

The optimal range for total is 6.9 to 7.4 g/dL. High levels may indicate a high protein diet, increased uric acid, or low HCL. Low levels under 6. 9. may indicate a low protein diet, liver dysfunction, or low HCL. Low HCL is commonly caused by an H pylori infection, gut inflammation, dysglycemia, or hypothyroidism.

Abnormal BUN

Blood urea nitrogen (BUN) is formed in the liver. It is the final step of protein metabolism. It is a waste product that your kidneys remove from your blood. High levels often indicate problems with kidney function. High BUN levels (over 21) can play a role in upper gastrointestinal bleeding.

The clinical range for BUN is 6 to 24 mg/dL. The optimal range is 13 to 18 mg/dL. High levels can be a kidney problem or high functional range levels often indicate low stomach acid or dehydration. If the BUN levels are high and your creatinine and phosphorus levels are high, it usually means kidney problems, while if only the BUN levels are high, it may be due to dehydration or low HCL.

High BUN and high albumin usually mean dehydration. Low levels under 13 may mean low HCL. Low levels can be too much hydration. Low BUN can also mean malnutrition, Celiac disease, or low HCL.

High or low MCV

MCV stands for the mean corpuscular volume and is the average volume of a red blood cell. Iron deficiency, vitamin deficiencies, and red blood cell problems often cause unhealthy MCV levels. Poor MCV can be linked to gut health issues as well.

Optimal levels of MCV are between 85 and 92 fl. Low MCV is related to a microcytic, or iron deficient, red blood cell. High MCV, over 92, is related to a megaloblastic, or a B vitamin deficient, red blood cell. If the MCV is flagged high it is typically a B12 or folate deficiency. If the MCV is flagged low it is typically an iron deficiency. Both of these can be related to poor absorption from low stomach acid levels.

Low chloride

Chloride is an essential electrolyte that affects fluid and pH balance. It is also a critical element in the development of HCL stomach acid. HCL is essential for digestion and taking care of pathogens from undigested food. Adrenal stress and adrenal failure are often behind low chloride levels, while stress, insulin resistance, or aspirin use are signs of higher levels.

The optimal range for chloride is 100 to 106 mmol/L. Elevated levels of chloride may be a sign of adrenal stress, high salt diets, kidney problems, or too much aspirin. Low levels of chloride, under 100, may indicate adrenal fatigue, low HCL, or kidney issues.

Low Zinc, B12 & Iron

Zinc is an important mineral that helps to reduce inflammation, improve immune health, and support overall health. Zinc supplementation may help to improve acid reflux and heartburn. It may also help reduce intestinal permeability in those with Crohn’s disease.

Vitamin B12 is important for brain and mental health, bone health, energy, heart health, and reduced risk of anemia. Gastric acid inhibitor medications for acid reflux and heartburn may cause a deficiency in vitamin B12. A 2014 review published in Cell Metabolism has found that vitamin B12 may serve as an important modulator for the gut microbiome.

Iron is essential for growth and development, energy, hormonal health, and other areas of your health. Lower gastric acid output related to an H. pylori infection may cause problems with iron absorption, which may lead to iron deficiency. Iron deficiency can cause gut microbiome issues, however, high or unabsorbed iron can too.

Normal plasma zinc is 90-135 ug/dL. Normal serum vitamin B12 level between 800 pg/mL and 1500 pg/mL. The lab range for serum iron is 27-159 ug/dL while the functional range is 85-130 ug/dL. Low zinc levels, under 90, low B12, under 800, low serum iron, under 85, may indicate low HCL levels and gut health issues.

Comprehensive blood analysis

To determine the optimal ranges of these markers, you may want to consider a Comprehensive Blood Analysis (CBA). This blood analysis is a very detailed blood test that looks at all of these markers of inflammation and other health functions.

This test is more sophisticated than most conventional doctors order. It examines all parameters for inflammation, blood sugar levels, insulin levels, immune system function, thyroid function, parathyroid hormone levels, mineral and electrolyte balance, zinc and copper ratio, vitamin A and D levels, folate and vitamin B12 levels, a complete metabolic panel, complete blood count, liver function, kidney function, urinary tract health, nutrient deficiencies, and more.

A CBS may be done regularly both as a preventative measure and to monitor your inflammation levels and progress if you are on a treatment plan.

Final thoughts

Leaky gut syndrome occurs when your gut lining has developed some holes that can allow undigested food particles, toxins, and microbes to pass through into your bloodstream. This can increase chronic inflammation and lead to a chronic immune response. Leaky gut syndrome can cause histamine intolerance, chronic symptoms, autoimmunity, and other chronic health issues.

If you have symptoms of leaky gut syndrome or histamine intolerance, you may want to consider testing- you can get a discounted gut zoomer at a discounted price as a member of WellnessPlus HERE.

 

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