The Keystone Approach

1. Autoimmune Disease Originates in the Gut

"A lot of doctors and people may think that leaky gut itself is sort of a froufrou alternative concept,” but “the real name is ‘increased intestinal permeability,’ and it is a definitive, scientific fact.”

The hidden truth. For too long, autoimmune diseases like psoriasis and arthritis have been treated as isolated conditions, with treatments focusing solely on suppressing symptoms. However, emerging science reveals a profound connection between gut health and systemic inflammation, positioning the gut as the true origin of many autoimmune conditions. This paradigm shift opens doors to addressing root causes rather than just managing symptoms.

Leaky gut's role. A compromised intestinal barrier, often called "leaky gut," is a common underlying factor. When the gut lining is damaged, it allows bacteria, toxins (like lipopolysaccharide or LPS), and undigested food proteins to cross into the bloodstream. This triggers a massive immune response, not just locally in the gut, but systemically throughout the body, leading to inflammation in the skin and joints.

Spondyloarthropathy family. This gut-autoimmunity link is particularly strong in the spondyloarthropathy family of diseases, which includes:

• Psoriasis/Psoriatic Arthritis
• Ankylosing Spondylitis
• Juvenile Idiopathic Arthritis
• Crohn’s Disease
• Ulcerative Colitis
• Uveitis

These conditions often show microscopic gut inflammation resembling early Crohn's disease, even without overt bowel symptoms, highlighting the gut's central role.

2. Microbiome Imbalance Fuels Systemic Inflammation

"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis."

The delicate balance. Our gut hosts trillions of microbes, a complex ecosystem known as the microbiome. In autoimmune conditions, this ecosystem is often imbalanced, characterized by a depletion of beneficial species and an overgrowth of harmful ones. This dysbiosis directly impacts immune regulation, pushing the body towards an inflammatory state.

Beneficial microbes' role. Key "keystone" species, particularly from Clostridia clusters IV and XIVa (e.g., Faecalibacterium prausnitzii), are often depleted in autoimmune patients. These microbes are crucial because they produce butyrate, a short-chain fatty acid that:

• Feeds intestinal cells
• Induces regulatory T cells (Tregs)
• Calms the immune system

Without enough of these, the immune system loses a vital control mechanism.

Harmful microbes' impact. Conversely, an excess of inflammatory species like E. coli, Klebsiella, Streptococcus, and Proteus mirabilis exacerbates the problem. These pathogens damage the gut barrier and produce toxins like LPS, activating immune cells (Th17 cells) that drive inflammation in autoimmune diseases. Specific links include Prevotella in rheumatoid arthritis and adherent-invasive E. coli in spondyloarthritis.

3. Probiotics: Key to Rebalancing Your Gut Ecosystem

"Probiotics are one of the best tools we have to rebalance the microbiome."

Strategic rebalancing. Probiotics offer a powerful, low-risk way to restore gut harmony. They work by both boosting beneficial bacteria and suppressing harmful species, effectively shifting the microbiome towards an anti-inflammatory state. This can lead to significant improvements in autoimmune symptoms.

Supporting the good. Certain probiotic species excel at nurturing our native beneficial microbes. Bifidobacteria (B. infantis, B. longum, B. breve) are keystone species that produce acetate, a preferred food source for butyrate-producing bacteria. Lactobacillus rhamnosus GG (Culturelle) also significantly increases butyrate-producing strains, helping to calm the immune system.

Suppressing the bad. Many probiotics directly inhibit pathogens by competing for nutrients and altering gut acidity. For a more aggressive approach, advanced pathogen-fighting strains like BioK+ (a blend of L. acidophilus, L. casei, L. rhamnosus), Mutaflor (E. coli Nissle 1917), and Florastor (Saccharomyces boulardii) produce specific antimicrobial compounds and block pathogen adhesion, making them invaluable for tackling stubborn overgrowths.

4. Beyond Probiotics: Targeted Strategies for Gut Healing

"To give the MMC as much opportunity as possible to do its important job, it is best to eat only at defined meal times."

Holistic gut support. While probiotics are foundational, a comprehensive approach to gut healing involves several other strategies to combat bacterial overgrowth and strengthen the intestinal barrier. These measures address the underlying mechanisms that prevent a healthy gut environment.

Optimizing digestion. Proper digestive function is crucial.

• Meal spacing: Eating only at defined times (4-5 hours apart, no snacking) allows the Migrating Motor Complex (MMC) to perform its "cleaning cycle" in the small intestine, preventing bacterial buildup.
• Digestive support: Adequate stomach acid, enzymes, and bile salts are essential. Bile, in particular, suppresses undesirable bacteria and reduces the absorption of inflammatory toxins like LPS. Supplements like ox bile or betaine HCL can be beneficial.
• Prokinetics: Agents like ginger or Iberogast can stimulate the MMC, promoting gut motility and preventing stagnation that leads to SIBO.

Natural antimicrobials. For persistent overgrowths, short-term use of targeted natural antimicrobials can be effective without broadly harming beneficial species.

• Lactoferrin: An iron-binding protein effective against Klebsiella and E. coli, also boosts Bifidobacteria.
• Allicin (from garlic): Potent against Streptococcus, Proteus mirabilis, E. coli, Klebsiella, and Candida.
• Berberine: Inhibits Klebsiella, Streptococcus, Candida, E. coli, and boosts butyrate producers.

These strategies, combined with dietary changes, create a powerful defense against gut dysbiosis.

5. The Keystone Diet: Starve Pathogens, Nourish Beneficial Microbes

"If instead we adopt a diet based on highly processed grains and sugars, we effectively starve our most important gut bacteria, while allowing unwanted species to take over."

Food as medicine. The food we eat profoundly shapes our microbiome. The Keystone Diet focuses on starving harmful, inflammatory microbes while providing ample nourishment for beneficial, immune-regulating species. This involves a strategic reduction of starches and sugars, coupled with an emphasis on nutrient-dense, anti-inflammatory foods.

The low-starch imperative. Eliminating or significantly reducing starch and sugar is particularly effective for conditions linked to starch-loving bacteria (e.g., Klebsiella, adherent-invasive E. coli), such as ankylosing spondylitis, psoriatic arthritis, and inflammatory bowel disease. This approach has a long history of success in reducing inflammation and promoting gut healing, as seen in the Specific Carbohydrate Diet (SCD) for IBD.

Mediterranean foundation. The overall diet leans heavily on Mediterranean principles:

• High fiber: From a wide variety of non-starchy fruits and vegetables (especially cruciferous vegetables, apples, pears). This feeds beneficial bacteria and boosts butyrate production.
• Polyphenols: Found in darkly pigmented fruits (cranberry, pomegranate, blueberries) enhance beneficial Akkermansia muciniphila, which strengthens the gut barrier.
• Lean proteins: Chicken, fish, lean pork, grass-fed beef.
• Healthy fats: Primarily olive oil and avocado oil.

By adopting these principles, the Keystone Diet provides the essential building blocks for a balanced microbiome and a calm immune system.

6. Anti-Inflammatory Fats: The Mediterranean Advantage

"The fats at the core of Mediterranean diet have an extraordinary ability to reduce inflammation."

Strategic fat choices. Not all fats are created equal when it comes to inflammation. The Keystone Diet emphasizes fats proven to calm the immune system, primarily those found in the Mediterranean diet, while minimizing inflammatory fats.

The power duo: Fish and olive oil.

• Fish: Rich in EPA and DHA omega-3 fats, which directly inhibit inflammatory mediators. Aim for 2-3 servings per week of low-mercury, high omega-3 fish like salmon, sardines, Atlantic mackerel.
• Olive oil: Extra-virgin olive oil contains powerful antioxidant compounds that protect against oxidative damage and suppress inflammatory mediators. It's stable for cooking at moderate temperatures.
• Avocado oil: Similar to olive oil, rich in monounsaturated fats and antioxidants.

These fats work synergistically to reduce systemic inflammation, leading to milder autoimmune symptoms.

Fats to avoid.

• Refined seed oils: Canola, soy, sunflower oils are high in unstable polyunsaturated fats that readily oxidize when heated, contributing to inflammation.
• Saturated fats: Found in coconut oil, ghee, butter, and fatty animal products. Recent research shows saturated fats activate key immune receptors (TLR4, NLRP3) and trigger inflammatory cytokine release. Coconut oil may also facilitate the transport of bacterial toxins across the gut barrier.
• High omega-6 fats: While some omega-6s are fine, high levels of arachidonic acid (in fatty pork, organ meats, farmed tilapia) can exacerbate inflammation.

By making conscious choices about fats, you can significantly impact your body's inflammatory response.

7. Customizing Your Diet: Identifying Personal Triggers

"The only way to know how they affect you is to eliminate them for one or two months, then gradually reintroduce each food while carefully observing your response."

Beyond general guidelines. While the core Keystone Diet provides a strong anti-inflammatory foundation, individual sensitivities can vary. A crucial step in optimizing your healing journey is to identify your unique "trigger foods" through a systematic elimination and reintroduction process.

Common culprits. Focus on foods known to cause sensitivities in some autoimmune patients:

• Common allergens: Dairy, eggs, nuts, wheat (already eliminated in Level 1), soy, corn, shellfish.
• Nightshades: Tomatoes, potatoes (already eliminated in Level 1), bell peppers, chili peppers (and spices like paprika, cayenne), eggplant, goji berries. These contain glycoalkaloids and lectins that can damage the gut barrier and activate mast cells.

The elimination process. Eliminate suspected foods for 1-2 months, then reintroduce them one at a time, observing for any return of symptoms (joint pain, skin flares, digestive issues, headaches, fatigue). This personalized approach helps you build a sustainable diet tailored to your body's needs.

Food chemical sensitivities. If you react to a wide array of foods inconsistently, you might have an intolerance to natural food chemicals like histamines or salicylates. This is often linked to SIBO or pathogen overgrowth, which can heighten mast cell activity. Addressing gut dysbiosis and supplementing with high-dose vitamin C can help reduce these sensitivities.

8. Essential Supplements to Fine-Tune Immunity

"Vitamin D deficiency is also correlated with disease activity: those with the lowest levels have the most severe symptoms."

Targeted support. Beyond diet and probiotics, specific supplements can provide additional support to regulate the immune system, reduce inflammation, and promote healing. These are optional but can make an incremental difference.

Key supplements:

• Vitamin D: Crucial for immune regulation and bone health. Deficiency is common in autoimmune patients and correlates with disease severity. High doses (e.g., 5000 IU/day short-term, 2000 IU/day maintenance) can significantly improve psoriasis and arthritis symptoms.
• Glucosamine: A building block for cartilage and joint fluid. While primarily studied for osteoarthritis, it can reduce cartilage-degrading enzymes (MMP-3) in rheumatoid arthritis, suggesting broader benefits for joint protection.
• Meriva (Curcumin): A highly absorbed form of turmeric's active compounds. Standard curcumin is poorly absorbed, but Meriva has shown promise in reducing joint pain, inflammation, and improving conditions like psoriasis and uveitis. It may also positively impact the microbiome and gut barrier.
• Gamma-Linolenic Acid (GLA): Found in borage or evening primrose oil, GLA inhibits inflammatory mediators like leukotriene B4, which is particularly relevant in psoriasis. It's best taken with fish oil to prevent potential increases in arachidonic acid.

Always consult your doctor before starting new supplements, especially given the lack of regulation in the industry.

9. Low-Dose Naltrexone: A Novel Immune Regulator

"This newly discovered mechanism is entirely separate from the opioid/endorphin system. It is instead based on the fact that naltrexone can directly interfere with the activation of immune cells by bacterial toxins such as lipopolysaccharide."

Repurposing a drug. Naltrexone, traditionally used for opioid addiction, has shown remarkable promise in very low doses (LDN) as an immune system modulator for inflammatory diseases. Its ability to regulate immunity and reduce pain makes it a compelling option for many autoimmune conditions.

Mechanism of action. LDN's anti-inflammatory effects stem from its ability to block the TLR4 receptor on immune cells. This receptor normally detects bacterial toxins like LPS, triggering an inflammatory cascade. By "blindfolding" these cells, LDN prevents them from overreacting to bacterial by-products, thereby calming the immune system. This mechanism is highly relevant to psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis, where TLR4 plays a significant role.

Clinical evidence. Double-blind, placebo-controlled trials in Crohn's disease have demonstrated LDN's ability to induce significant intestinal healing and remission. Studies in multiple sclerosis and fibromyalgia also show reductions in pain and improved quality of life. LDN's effectiveness in reducing inflammation, as indicated by markers like ESR, suggests its broad applicability across various autoimmune conditions.

Practical considerations. LDN is prescribed off-label by compounding pharmacies in low doses (1.5-4.5 mg). Side effects are generally mild (headache, vivid dreams) and can be minimized by starting with a low dose. It can be used alongside conventional medications like methotrexate and biologics, offering a complementary approach to treatment.

10. Your Personalized Path to Autoimmune Healing

"The Keystone Approach is thus designed to help you discover which factors make the most difference in your particular case."

Empowering your journey. Healing from autoimmune disease is a personal journey, and the Keystone Approach provides a flexible, evidence-based framework to guide you. It acknowledges that while core principles apply to all, individual responses to diet and supplements will vary, necessitating a personalized strategy.

The basic plan. Start with foundational changes:

• Diet: Emphasize high-fiber, antioxidant-rich vegetables, fish, lean meats, and olive oil. Adopt Level 1 low-starch (eliminate gluten, corn, soy, peanuts, quinoa, potatoes; limit other starches to 2 servings/day; cut added sugar). Space meals 4 hours apart.
• Supplements: Introduce a Level 1 probiotic (e.g., L. rhamnosus GG, B. infantis), 2000 IU Vitamin D3, and 2-4g EPA+DHA fish oil (on non-fish days).

Progressive customization. If symptoms persist, advance to stricter dietary levels (Intermediate or Advanced low-starch) or explore troubleshooting steps like eliminating common allergens (dairy, eggs, nuts) and nightshades. Laboratory testing (stool, breath, allergy) can provide valuable insights, but careful observation of your body's response remains paramount. The goal is to find your unique tolerance levels and build a sustainable, anti-inflammatory lifestyle.

Last updated: January 24, 2026