While leaky gut syndrome has not been universally established as a distinct medical condition, its concept remains a topic of considerable interest and discussion within the scientific community.
Mounting evidence suggests increased intestinal permeability may contribute to various chronic health issues. Therefore, there is a growing interest in exploring ways to support gut health in individuals experiencing typical gastrointestinal discomfort and systemic inflammation symptoms.
This article will provide a comprehensive overview of approaches that may support gut health, offering insights into testing modalities, dietary and lifestyle considerations, and supportive strategies to promote overall well-being.
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What Is Leaky Gut?
Leaky gut refers to the loosening of the tight junctions between the cells that line the small intestine.
Under typical conditions, the small intestinal barrier exhibits selective permeability. This means it permits the passage of small, digested proteins, nutrients, and water into the bloodstream while blocking the passage of larger, undigested molecules.
Leaky gut is a state characterized by increased permeability. This is how it develops:
- Small intestinal cells are linked together by proteins called tight junctions.
- Inflammatory triggers can lead to the breakdown of these proteins, effectively creating larger spaces between the small intestinal cells.
- Once this happens, a leaky gut may allow large molecules (like undigested food particles, microbes, and toxins) to pass through the intestinal barrier, potentially leading to issues in and beyond the digestive tract.
Leaky Gut Signs & Symptoms
Leaky gut may be associated with a wide array of symptoms across multiple body systems:
- Digestive: abdominal discomfort, gas, bloating, constipation, diarrhea
- Neurological: headache, anxiety, mood changes, brain fog, fatigue
- Musculoskeletal: joint discomfort
- Skin: acne, rashes, eczema, psoriasis
Research also suggests that leaky gut may play a role in the development and progression of chronic conditions, including:
- Allergies
- Alzheimer's disease
- Arthritis
- Asthma
- Autism
- Autoimmune conditions: celiac disease, inflammatory bowel disease, lupus, multiple sclerosis, rheumatoid arthritis, type 1 diabetes
- Chronic fatigue syndrome
- Fibromyalgia
- Liver conditions
- Obesity (5, 8, 33, 45)
Root Causes of Leaky Gut
Zonulin is a protein secreted by the intestinal tract and is currently the only known protein that reversibly regulates intestinal permeability by controlling the tight junctions between epithelial cells. Environmental triggers and lifestyle factors can stimulate the upregulation of zonulin, potentially increasing intestinal permeability. (32)
Lifestyle
Medications: Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapy agents, radiation therapy, oral contraceptive pills, and frequent antibiotic use may contribute to leaky gut by inducing intestinal inflammation and decreasing diversity within the gut microbiome. (23)
Diet: Western diets, characterized by excessive inflammatory foods (i.e., refined sugars, saturated/trans fats, alcohol) and insufficient fiber, may increase intestinal inflammation and dysbiosis (2). The wheat protein gliadin can directly upregulate zonulin and may contribute to leaky gut. This mechanism is suspected to contribute to the development of celiac disease.
Stress: Emotional and physical stress can influence nervous system function and increase stress hormones, which may contribute to leaky gut. Chronic, unresolved stress may induce intestinal dysbiotic patterns and prevent healing pathways, making it more difficult for the body to restore an intact intestinal barrier. (25, 42, 57)
Poor Sleep: Sleep deprivation may adversely affect the gut microbiota, which can exacerbate gut barrier dysfunction and contribute to the development of leaky gut syndrome.
Dysbiosis
Intestinal dysbiosis (an imbalance of microbes in the gut) may increase zonulin production and stimulate intestinal permeability (32). Dysbiosis can negatively impact the neural, hormonal, and immune mechanisms influencing gut permeability (51). Dysbiosis is associated with intestinal dysmotility and gastrointestinal symptoms.
Environmental Toxins
Exposure to environmental toxins, including bisphenols, phthalates, heavy metals, and pesticides, may contribute to increased oxidative stress, inflammatory responses, disruptions in healthy hormonal signaling, and imbalances in the gut microbiome. Together, these interruptions may contribute to the progression of leaky gut.
How to Diagnose Leaky Gut
Doctors may assess leaky gut through medical history evaluation, symptom assessment, and laboratory tests.
Step 1: Leaky Gut Testing
Lab tests for intestinal permeability may measure zonulin or the lactulose-to-mannitol ratio (LMR).
Zonulin
Fecal zonulin is a direct measurement of the mucosal production of zonulin. However, due to notable intraday fluctuations, concerns arise regarding the accuracy of this collection method. To address this, researchers suggest assessing IgA and IgG antibodies against zonulin, which are more stable and potentially provide a more precise evaluation of intestinal permeability. (20)
These zonulin tests are available to order through Rupa Health:
- Zonulin by Diagnostic Solutions
- Zonulin Add-On by KBMO Diagnostics
LMR
Lactulose and mannitol are two sugar molecules of different sizes. When ingested orally, they pass through the intestinal barrier. However, if the barrier is compromised, larger molecules like lactulose may pass through more easily, leading to an elevated LMR in urine samples collected after ingestion. This ratio serves as an indicator of increased intestinal permeability, suggesting potential issues with gut barrier function. (20)
The Intestinal Permeability Assessment by Genova Diagnostics measures the urinary LMR.
Step 2: Testing to Uncover Root Causes of Leaky Gut
Once the presence of leaky gut has been considered, additional testing may be helpful to identify the underlying triggers for increased permeability. These labs can help guide doctors in personalizing approaches and may include comprehensive gastrointestinal, stress, food sensitivity, and environmental toxin testing. The decision to order these various labs can be guided by patient history and the symptoms they present with.
These panels can be an excellent starting point:
- GI-MAP by Diagnostic Solutions
- trio-smart SIBO Breath Test by Gemelli Biotech
- Adrenal Function Profile by Doctor's Data
- IgG Food MAP with Candida + Yeast by Mosaic Diagnostics
- RTL Tox Complete by RealTime Laboratories
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Approaches to Support Gut Health
There are various ways to support gut health and promote overall well-being. The 5-R protocol is a framework used to support gut health by identifying, addressing, and promoting gut-related wellness. Strategies used in this protocol include dietary changes, lifestyle modifications, and supportive supplements.
1. Remove
Here's Why This Is Important:
This phase involves identifying and addressing potential triggers such as inflammatory foods, pathogens, toxins, and stressors that may affect the gut lining. By addressing these underlying factors, the "remove phase" creates a favorable environment for the subsequent steps of the protocol, allowing for effective support and promotion of gut health.
How Do You Do This?
Several steps can be taken to address factors contributing to gut dysfunction. A thorough patient history and lab results can help guide recommendations.
- Trigger Foods: Identify and consider eliminating foods that may be triggering inflammation or sensitivity reactions in the gut. Common culprits include wheat, milk, peanuts, soy, egg, corn, and processed foods.
- Address Gut Infections: Consider testing for and addressing gut infections, including bacterial overgrowth, parasites, or fungal overgrowth. This can involve using prescription medications or antimicrobial herbs, such as berberine, oregano, neem, and garlic.
- Reduce Toxin Exposure: Minimize exposure to environmental toxins and harmful substances that can disrupt gut health. This includes avoiding cigarette smoke, eating organic produce, drinking filtered water, and using air purifiers whenever possible.
- Manage Stress: Implement stress-reducing techniques such as meditation, deep breathing exercises, yoga, or mindfulness practices.
2. Replace
Here's Why This Is Important:
The "replace phase" of the 5-R gut health protocol focuses on supporting optimal digestive function by replenishing beneficial substances that support gut health. This phase lays the foundation for effective support and gut restoration, which are the focus of the next steps in the protocol.
How Do You Do This?
This step involves reintroducing essential enzymes required for proper digestion and nutrient absorption. Digestive enzyme supplements often include one or more of the following ingredients to enhance the digestion of carbohydrates, proteins, and fats:
- Hydrochloric acid
- Pepsin
- Amylases
- Proteases
- Lactase
- Lipase
- Ox bile
Nutrient support can also be initiated during this phase for individuals with nutrient deficiencies secondary to malabsorption or restricted diets. A high-quality multivitamin/mineral supplement provides essential micronutrients required by the body for optimal gut health and general well-being.
3. Reinoculate
Here's Why This Is Important:
The "reinoculate phase" focuses on replenishing and diversifying the beneficial bacteria in the gut microbiome to restore balance in the microbial community. A healthy gut microbiome is essential for optimal digestion, nutrient absorption, immune function, and overall health.
How Do You Do This?
Reinoculation can be achieved with probiotic supplements or fermented foods like yogurt, kimchi, sauerkraut, or pickles. Lactobacillus spp., Bifidobacterium spp., and Saccharomyces boulardii are commonly utilized probiotics to support digestive health and function.
4. Repair
Here's Why This Is Important:
The "repair phase" focuses on supporting the integrity of the intestinal lining by promoting mucosal health, reducing inflammation, and encouraging tissue regeneration.
How Do You Do This?
Supporting the gut lining takes time, but various supplements have been shown to help maintain intestinal permeability and support the healing process.
- Vitamin D may modulate the expression of tight junction proteins and the immune system, thereby supporting intestinal permeability. 2,000 IU daily has been shown to support intestinal permeability.
- L-glutamine is an amino acid and the preferred fuel source for the cells lining the intestines. A substantial pool of evidence supports its intestinal health properties. Doses can range from 15-45 grams daily. (37, 40)
- Omega-3 polyunsaturated fatty acids 1,000-3,000 mg daily
- Zinc carnosine 50 mg twice daily
Just as inflammatory diets can perpetuate leaky gut, an anti-inflammatory diet rich in nutrient-dense foods can support mucosal health and reduce inflammation. This includes:
- Bone broth is rich in amino acids, collagen, and minerals that support gut health and repair
- Omega-3-rich foods, including fatty fish, flaxseeds, chia seeds, and walnuts
- Colorful fruits and vegetables are rich in antioxidants and phytonutrients that help reduce inflammation, support tissue repair, and nourish a healthy gut microbiome
- Fiber-rich foods: soluble fiber from foods like oats, apples, and beans can help support a healthy gut microbiome
5. Rebalance
Here's Why This Is Important:
This phase aims to sustain the progress made during the protocol by promoting a balanced and supportive environment for ongoing gut health. By incorporating lifestyle modifications, dietary adjustments, stress management techniques, and regular monitoring, this final phase helps maintain long-term intestinal wellness.
How Do You Do This?
This is an ongoing process that focuses on forming sustainable, gut-healthy habits:
- Get sufficient, good-quality sleep every night. Implement habits that support optimal sleep, such as having a consistent bed- and wake-up time every day, avoiding caffeine in the afternoon/evening, and turning off screens at least one hour before bed. Individuals who continue to experience sleep disturbances despite having good sleep hygiene should discuss diagnostic testing and options for sleep support with a healthcare provider.
- Continue to eat a well-balanced, anti-inflammatory diet
- Exercise regularly. Evidence suggests that getting three hours of moderate-intensity weekly may support gut health.
- When possible, address stressors in your life. Mind-body practices, such as yoga, deep breathing, and meditation, can help reorient to unavoidable stressors so that they have less of a negative impact on mental, emotional, and physical health.
The Risks of Untreated Leaky Gut
When the intestinal barrier becomes compromised, undigested food particles, toxins, and bacteria may pass into the bloodstream, potentially triggering an immune response. This immune reaction may result in the release of inflammatory molecules that could initiate and sustain inflammation throughout the body.
Chronic inflammation may affect tissues and organs, potentially contributing to the development of numerous health conditions, including autoimmune diseases, metabolic disorders, cardiovascular diseases, neurodegenerative diseases, and cancer. (19, 49)
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Key Takeaways:
- Leaky gut involves the disruption of the intestinal barrier, which may lead to chronic inflammation and dysregulation of the immune system, potentially contributing to the development of various chronic conditions.
- The good news is that the intestinal barrier may be supported by addressing underlying factors that may predispose someone to leaky gut, including poor diet, chronic stress, and gut dysbiosis. Comprehensive testing, which identifies specific triggers, plays a role in effective support.
- Healthcare practitioners can develop targeted interventions to support gut health and mitigate the systemic effects of leaky gut. Ultimately, a multifaceted approach combining dietary modifications, lifestyle interventions, targeted supplementation, and personalized strategies offers the best chance to support gut health and promote long-term wellness.
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