Leaky Gut Syndrome
What is Leaky Gut Syndrome?
Leaky gut is sometimes referred to as intestinal permeability, which means that the cells in the intestinal lining are “leaky” or “perforated” - meaning that there are microscopic “gaps” in the gut lining
Under normal circumstances, the cells of the intestinal lining are tightly packed, forming a barrier. When there is intestinal permeability, pathogens, toxins or partially digested food can “leak” through, into the bloodstream.
The immune system attacks these “invaders” and the result is inflammation. This can result in an overactive immune system, on high alert all the time and reacting to benign things, even the body’s own tissues, which can lead to autoimmune conditions.
Inflammation associated with leaky gut produces gastrointestinal symptoms commonly seen in ASD like GI pain, bloating, and poor digestion (see: GI Issues). It can also create neurological problems like brain fog and ADHD-like behaviors.
Zonulin is a protein that is increased when intestinal permeability is present. It can be measured in select comprehensive stool panels (such as the GI-MAP) as a biomarker for leaky gut.
Fortunately, the cells of the intestines regenerate quickly so removing the potential causes and addressing underlying issues can result in gut healing and reformation of those tight junctions between cells. (See “Next Steps” section below for guidance on supplements, diet, and lifestyle)
There is evidence of low-grade GI inflammation in a subgroup of children with ASD that is not present in neurotypical children with similar GI symptoms. The loss of gut barrier function may not be a generalizable phenomenon among children with ASD, but instead could involve a subgroup of patients with ASD. [5]
Signs & Symptoms
Digestive issues like gas, bloating, pain, constipation, diarrhea
Food allergies, sensitivities, or intolerances (see: Food Reactions)
Mood issues like depression or anxiety
Skin issues like eczema
Autoimmune conditions
Contributing Factors
Inflammatory foods (like gluten, dairy) or individualized food sensitivities
Intestinal infections (see: dysbiosis or yeast overgrowth)
Toxins like pesticides (like glyphosate), plastic residues, heavy metals, etc.
Trauma such as invasive surgery or endotoxemia
Certain medications like aspirin and NSAIDs
Chronic stress
Certain nutrient deficiencies may increase risk (vitamin D, zinc, vitamin A, etc)
Alcohol
Testing for Leaky Gut
There are a few different ways to test for Leaky Gut. While these tests are helpful to identify Leaky Gut, it doesn’t tell any information about the root cause. Because of this, we recommend running other diagnostic tests such as a comprehensive stool panel (like GI-MAP), food sensitivities, nutrient deficiencies, toxic load, and testing for Celiac Disease, among others suggested by your healthcare provider.
Measure Zonulin Levels [1,4]
Zonulin can be measured through stool and serum. We prefer stool testing and often use the GI-MAP (be sure to have your provider to select Zonulin as an add-on), but it can also be tested by Vibrant America’s Gut Zoomer.
The higher the level of zonulin, the more severe the intestinal permeability. GI-MAP indicates 107 ng/g or above as leaky gut positive, though levels 70+ typically indicate treatment.
Differential Sugar Test (Lactulose & Mannitol Test) [1]
This is a urine test that measures the level and ratio of two sugars to determine if the gut is allowing these molecules to pass through. In a healthy gut, the sugars should not be able to pass through since the molecules are too large. In a leaky gut, they will be able to pass through. There is some controversy over the accuracy and validity of this test. It has been used since the 1970s as a marker for intestinal permeability.
Antibody Testing
LPS Antibodies: LPS is a component of certain gram-negative bacteria. It is typically too large of a substance to pass through the gut barrier, but it can if the gut is leaky. If LPS crosses the intestinal barrier, the body will make antibodies against it. The presence of LPS antibodies indicates leaky gut positive.
Occludin Antibodies: Measures antibodies to a protein, occludin, that makes up tight-junctions between gut cells. If occludin crosses the intestinal barrier, the body will make antibodies against it. The presence of occludin antibodies indicates leaky gut positive.
Actomyosin Network Antibodies: Similar to occludin, actomyosin is found in tight-junctions between gut cells. If actomyosin crosses the intestinal barrier, the body will make antibodies against it. The presence of actomyosin antibodies indicates leaky gut positive.
Next Steps
Diet
Identify and remove food sensitivities to decrease inflammation, calm the immune system, and allow the gut to heal.
Certain foods are naturally inflammatory, such as simple starches (see: carbohydrates), cane sugar, artificial ingredients, and MSG.
Other foods may be uniquely inflammatory to the person.
Some of the most common foods that cause gut inflammation due to sensitivities are gluten, dairy, soy, and corn.
Gluten, in particular, may contribute to intestinal permeability due to a protein it contains called gliadin. A gluten-free diet may be indicated.
Consider if any current medications are contributing to leaky gut, such as NSAIDs or chronic use of antibiotics.
Increase foods rich in antioxidants such as berries, leafy greens, and dark chocolates. Antioxidant supplements include glutathione, vitamin E, and CoQ10, among others.
Supplements
A comprehensive multivitamin if the child is a picky eater, to replete nutrient levels. If the child has a nutritious diet, consider supplementing with vitamin D, zinc, and vitamin A, as these are important for gut barrier health.
Support immune health and a strong, diverse microbiome with probiotics and prebiotics
Support optimal digestion and nutrient absorption with digestive enzymes
Support gut healing and address underlying issues (such as dysbiosis or yeast overgrowth) with certain herbs or supplements such as marshmallow root, aloe vera, L-glutamine, licorice root, collagen, bone broth, etc.
Consider Saccharomyces boulardii, a beneficial yeast that may help strengthen the gut lining
Fish oil may benefit leaky gut, though more studies are needed.
Antioxidants
Glutathione can help bind toxins and heavy metals to excrete them.
Alpha-lipoic acid can renew other antioxidants in the body which promotes detox
Lifestyle
Consider Toxic Load, and take next steps to reduce toxins in the environment
Reduce stress by implementing practices like yoga, meditation, etc. Yes, even kids with autism can participate and benefit, but it will look different for everyone.
Get as much time outside as possible, ideally 30+ minutes. Going on walks, jumping on the trampoline, or other forms of physical activity are great!
DISCLAIMER: Before starting any supplement or medication, always consult with your healthcare provider to ensure it is a good fit for your child. Dosage can vary based on age, weight, gender, and current diet.
Leaky Gut & Autism in the Research
Autism & Leaky Gut
Low-mild gut inflammation and augmented intestinal permeability were demonstrated together with the presence of GI symptoms. [2]
There is evidence of low-grade GI inflammation in a subgroup of children with ASD that is not present in neurotypical children with similar GI symptoms. The loss of gut barrier function may not be a generalizable phenomenon among children with ASD, but instead could involve a subgroup of patients with ASD. [5]
Leaky Gut & The Brain
Leaky gut allows bacterial metabolites to cross the gut barrier, impacting neurodevelopment during early childhood in susceptible subjects by way of the gut-brain axis. The “leaky gut” affects brain function, potentially contributing to the pathogenesis of ASD. [1]
The bacterial-derived short-chain fatty acids may serve as a fuel source for enterocytes lining the intestinal system. These chemicals can also result in a leaky gut that allows for more metabolites and bacteria to pass through the epithelial barrier, which can lead to detrimental neurologic effects. [3]
Research suggests a bidirectional communication between the gut and the brain, linking a microbiome-induced increased gut permeability to exaggerated entry of commensal bacteria into the bloodstream where they could stimulate faulty immune regulation and, ultimately, neuroinflammation typical of ASD. [5]
In the ASD brain, there is an altered expression of genes associated with blood-brain barrier integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. [6]
The microbiota and its metabolites are crucial in maintaining epithelial barrier integrity; therefore, dysbiosis in ASD patients may alter gut permeability. This condition, called “leaky gut”, may allow the passage of bacteria, toxins such as LPS and metabolites that activate the immune response and induce an inflammatory state into the bloodstream. The activated immune system releases inflammatory cytokines and chemokines, which can modulate the central nervous system and contribute to the pathogenesis of autism by influencing the early stages of brain development. [7]
An increase in short-chain fatty acids and 5′-HT-producing bacteria was observed in several studies on ASD patients. Increased levels of 5′-HT lead to tryptophan depletion (resulting in worsening repetitive behaviors) and hyperserotoninemia, which may affect GI symptoms. Moreover, some ASDs are even characterized by higher levels of intestinal permeability which allow passive diffusion of bacteria-derived lipopolysaccharides (LPS) and metabolites through the intestinal barrier. As a consequence, an increase in pro-inflammatory cytokines was observed, which are associated with impaired social communication and neurodevelopmental disorders. [8]
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[1] Fowlie G, Cohen N, Ming X. The Perturbance of Microbiome and Gut-Brain Axis in Autism Spectrum Disorders. Int J Mol Sci. 2018;19(8):E2251.
[2] Iovene MR, Bombace F, Maresca R, et al. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. 2017;182(3-4):349-63.
[3] Rosenfeld CS. Microbiome Disturbances and Autism Spectrum Disorders. Drug Metab Dispos. 2015;43(10):1557-71.
[4] Esnafoglu E, Cırrık S, Ayyıldız SN, et al. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J Pediatr. 2017;188:240-4.
[5] Fasano A, Hill I. Serum Zonulin, Gut Permeability, and the Pathogenesis of Autism Spectrum Disorders: Cause, Effect, or an Epiphenomenon. J Pediatr. 2017;188:15-7.
[6] Fiorentino M, Sapone A, Senger S, et al. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016;7:49.
[7] Fattorusso A, Di Genova L, Dell'Isola GB, Mencaroni E, Esposito S. Autism Spectrum Disorders and the Gut Microbiota. Nutrients. 2019;11(3):E521.
[8] Ristori MV, Quagliariello A, Reddel S, et al. Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions. Nutrients. 2019;11(11):E2812.
Authors
Elisa Rocks, RDN
Brittyn Coleman, MS, RDN/LD, CLT
