HW functional medicine · 12 min read · 2,342 words

The 5R Gut Healing Protocol: Remove, Replace, Reinoculate, Repair, Rebalance

The gut is not just a tube that processes food. It is a living ecosystem — a mucosal interface between your inner world and the outer environment, housing trillions of microorganisms, producing neurotransmitters, training immune cells, and regulating inflammation throughout your entire body.

By William Le, PA-C

The 5R Gut Healing Protocol: Remove, Replace, Reinoculate, Repair, Rebalance

The gut is not just a tube that processes food. It is a living ecosystem — a mucosal interface between your inner world and the outer environment, housing trillions of microorganisms, producing neurotransmitters, training immune cells, and regulating inflammation throughout your entire body. When this ecosystem breaks down, the consequences ripple outward into every organ system: brain fog, joint pain, skin eruptions, hormonal chaos, autoimmune activation, mood disorders.

The 5R Protocol is the foundational framework of functional medicine gut restoration. Developed by the Institute for Functional Medicine, it provides a systematic, phased approach to healing the gastrointestinal tract. It is not a weekend cleanse. It is a 3-6 month commitment to rebuilding the terrain from the ground up.

Each phase builds on the previous one. Skip a phase, and the entire protocol weakens. Rush through it, and you will relapse. The gut took years to degrade. Give it months to rebuild.


Phase 1: REMOVE (Weeks 1-6)

Eliminate Inflammatory Triggers

The first step is subtraction. You cannot heal a wound while you keep reopening it.

Elimination Diet: Remove the most common inflammatory and antigenic foods for a minimum of 21-30 days:

  • Gluten — triggers zonulin release, increasing intestinal permeability even in non-celiacs (Fasano, 2011)
  • Dairy — casein (especially A1 beta-casein) is a common immune trigger; lactose fermentation feeds dysbiotic bacteria
  • Soy — often GMO, contains phytoestrogens and protease inhibitors
  • Corn — high glycemic, frequently contaminated with mycotoxins, often GMO
  • Eggs — lysozyme in egg whites can be antigenic, especially with compromised gut barrier
  • Refined sugar — feeds pathogenic bacteria and yeast, disrupts microbial diversity
  • Alcohol — directly damages intestinal epithelium and tight junctions
  • Processed seed oils — promote omega-6 driven inflammation

This is not a deprivation diet. Patients eat clean proteins (wild fish, pastured poultry, grass-fed meat), abundant vegetables, healthy fats (olive oil, avocado, coconut), nuts and seeds (if tolerated), and low-glycemic fruits like berries.

Antimicrobial Protocols for Dysbiosis

If stool testing (GI-MAP, GI Effects) reveals bacterial overgrowth, pathogenic bacteria, or opportunistic organisms, targeted antimicrobials are indicated:

  • Berberine 500mg 2-3x/day — broad-spectrum antimicrobial effective against bacteria, yeast, and parasites. Also improves insulin sensitivity and supports bile flow. As effective as metformin for blood sugar regulation in some studies (Yin et al., 2008).
  • Oregano oil (standardized to 60-75% carvacrol) — 200mg 2x/day with meals. Potent against gram-negative bacteria, Candida species, and SIBO organisms.
  • Caprylic acid 600-1200mg/day — medium-chain fatty acid from coconut that disrupts yeast cell membranes.

Parasite Protocols

If parasites are detected (Blastocystis hominis, Dientamoeba fragilis, Entamoeba histolytica, Giardia):

  • Mimosa pudica seed — 1-2 capsules 2x/day on an empty stomach. Forms a gel-like substance that physically traps parasites and their eggs. Works as a gut scrubber.
  • Black walnut hull — contains juglone, a naphthoquinone with antiparasitic and antifungal activity. Typically 500mg 2-3x/day for 2-week cycles.
  • Wormwood (Artemisia absinthium) — 200-300mg 2-3x/day. Traditional antiparasitic. Also effective against Blastocystis.
  • Standard herbal parasite protocols run 30-60 days, sometimes with pulsed dosing (2 weeks on, 1 week off) to catch different lifecycle stages.

Biofilm Disruption

Many pathogenic organisms protect themselves by forming biofilms — sticky polysaccharide matrices that shield bacteria from both antimicrobials and your immune system. You must break these films open before antimicrobials can work effectively.

  • NAC (N-acetyl cysteine) 600-900mg 2x/day — disrupts biofilm matrix, also supports glutathione production for detoxification
  • InterFase Plus (Klaire Labs) — a blend of chelating agents (EDTA) and enzymes that break down biofilm structures. Take on an empty stomach, 30 minutes before antimicrobials.
  • Lauricidin (monolaurin) — derived from lauric acid in coconut, disrupts lipid-coated biofilms

Timing matters: Take biofilm disruptors on an empty stomach, 30-60 minutes before antimicrobial agents.


Phase 2: REPLACE (Concurrent with Phase 1)

Restore Digestive Capacity

Many patients with chronic gut issues have depleted digestive secretions. Without adequate stomach acid, enzymes, and bile, food is not properly broken down. Undigested food particles ferment in the gut, feed the wrong bacteria, and trigger immune responses.

Signs of Low Stomach Acid (Hypochlorhydria):

  • Bloating within 30 minutes of eating
  • Feeling of food “sitting like a rock” in the stomach
  • Heartburn or GERD (paradoxically, most reflux is caused by too LITTLE acid, not too much)
  • Undigested food in stool
  • Brittle nails, hair loss
  • Iron or B12 deficiency despite adequate intake
  • Recurrent gut infections (acid is your first line of defense)

Testing:

  • Baking soda test (home screening): Drink 1/4 teaspoon baking soda in 4oz cold water on an empty stomach first thing in the morning. Adequate stomach acid should produce belching within 2-3 minutes. No belching after 5 minutes suggests low acid. This is a rough screening tool, not diagnostic.
  • Heidelberg pH capsule test — the gold standard. Patient swallows a pH-sensing capsule on a string. Measures real-time stomach acid production and rebound. Available through specialized functional medicine clinics.

Replacement Protocol:

  • Betaine HCl with Pepsin — start with 1 capsule (typically 500-650mg) at the beginning of a protein-containing meal. Increase by 1 capsule per meal until a warm sensation in the stomach is felt, then back off by 1 capsule. Therapeutic doses range from 1-7 capsules per meal. Contraindicated with active ulcers, gastritis, or NSAID use.
  • Pancreatic enzymes — full-spectrum digestive enzyme blend containing protease, lipase, amylase, and ideally DPP-IV (for residual gluten and casein digestion). Take at the start of each meal. Look for products providing at least 50,000 USP units of protease and 20,000 USP units of lipase per serving.
  • Ox bile 125-500mg per meal — critical for patients without a gallbladder or with sluggish bile flow. Bile emulsifies fats, enables fat-soluble vitamin absorption (A, D, E, K), and has its own antimicrobial properties in the small intestine.

Phase 3: REINOCULATE (Weeks 4-12+)

Replenish Beneficial Microbiota

Once the terrain has been cleared of pathogens and digestive capacity is restored, it is time to seed the gut with beneficial organisms.

Probiotics:

Choose strains based on clinical need, not just colony count. More CFU does not always mean better.

  • Lactobacillus species (L. rhamnosus GG, L. plantarum, L. acidophilus) — colonize the small intestine, produce lactic acid, support immune modulation. L. rhamnosus GG is the most studied probiotic strain in the world.
  • Bifidobacterium species (B. longum, B. lactis, B. infantis) — predominant in the large intestine, produce short-chain fatty acids, support mucosal immunity. B. infantis 35624 specifically shown to reduce IBS symptoms (Whorwell et al., 2006).
  • Saccharomyces boulardii — a beneficial yeast (not killed by antibiotics). Effective against C. difficile, Candida, traveler’s diarrhea, and antibiotic-associated diarrhea. 250-500mg 2x/day. Can be used during antimicrobial treatment.
  • Spore-based probiotics (Bacillus subtilis, Bacillus coagulans, Bacillus clausii) — survive stomach acid, colonize effectively, produce natural antimicrobials. MegaSporeBiotic is a well-researched spore-based formula. Studies show it can reduce serum LPS (endotoxin) by 42% in 30 days, indicating improved gut barrier function (McFarlin et al., 2017). Start low (1/4 capsule) and increase slowly — these are potent and can provoke die-off reactions.

Prebiotics (Food for Probiotics):

Introduce gradually to avoid gas and bloating, especially in SIBO patients:

  • FOS (fructooligosaccharides) — 2-5g/day. Found in garlic, onions, leeks, asparagus.
  • GOS (galactooligosaccharides) — specifically nourish Bifidobacterium. Well-tolerated even by some IBS patients.
  • PHGG (partially hydrolyzed guar gum) — 5-7g/day. One of the best-tolerated prebiotics. Produces butyrate. Can actually be used DURING SIBO treatment (unlike most prebiotics).
  • Arabinogalactan (from larch tree) — 1-3 tablespoons/day. Supports SIgA production and immune function. Also a gentle prebiotic.
  • Resistant starch — cooked and cooled rice or potatoes, green banana flour, raw potato starch. Feeds butyrate-producing bacteria in the colon.

Fermented Foods:

Introduce slowly once acute dysbiosis is resolved:

  • Sauerkraut (raw, unpasteurized) — start with 1 tablespoon per meal
  • Kimchi — diverse Lactobacillus strains
  • Kefir (coconut or goat milk for dairy-sensitive patients)
  • Kvass — fermented beet or bread beverage
  • Miso, tempeh — fermented soy (reintroduce only after elimination phase if tolerated)

Phase 4: REPAIR (Weeks 4-16+)

Rebuild the Mucosal Lining

This is where you actively repair the damaged intestinal wall — the single-cell-thick epithelial barrier that separates the contents of your gut from your bloodstream and immune system.

Core Repair Nutrients:

  • L-Glutamine 5-10g/day (divided into 2-3 doses) — the primary fuel source for enterocytes (intestinal lining cells). Maintains tight junction integrity. Can be taken as powder in water between meals. Higher doses (15-20g/day) may be used in severe permeability cases. Note: use cautiously in patients with cancer history, as glutamine fuels rapidly dividing cells.
  • Zinc Carnosine 75mg 2x/day — specifically studied for gut repair. Shown to reduce NSAID-induced intestinal damage by 75% (Mahmood et al., 2007). Stabilizes the mucosal lining, supports tight junction proteins.
  • DGL (Deglycyrrhizinated Licorice) 400-800mg before meals — soothes and coats the mucosal lining. The deglycyrrhizinated form removes glycyrrhizin, which can raise blood pressure. Stimulates mucus production.
  • Slippery Elm 400-500mg 2-3x/day — demulcent herb that forms a soothing film over the intestinal lining. Traditionally used by Native Americans for GI complaints.
  • Marshmallow Root 300-500mg 2-3x/day — another demulcent. Rich in mucilage that protects and soothes inflamed tissue.
  • Collagen Peptides 10-20g/day — provides glycine, proline, and hydroxyproline — the amino acid building blocks of connective tissue repair. Can be added to smoothies or broth.
  • Butyrate (as tributyrin) 300-600mg 2x/day — the preferred fuel source of colonocytes. Strengthens tight junctions, reduces inflammation, supports regulatory T-cells. Also produced endogenously from dietary fiber by commensal bacteria.
  • Vitamin A (retinyl palmitate) 5,000-10,000 IU/day — essential for mucosal immunity, epithelial cell differentiation, and SIgA production. Do not exceed 10,000 IU in women of childbearing age.
  • Vitamin D3 5,000 IU/day (adjust based on serum levels, target 50-70 ng/mL) — regulates tight junction protein expression, modulates gut immune responses, supports antimicrobial peptide production.

Phase 5: REBALANCE (Ongoing)

Address the Root Cause Behind the Root Cause

The gut does not degrade in a vacuum. Chronic stress, poor sleep, and sympathetic nervous system dominance shut down digestive function at a fundamental level. You can take every supplement in the world, but if your nervous system is locked in fight-or-flight, your gut will not heal.

Vagus Nerve Activation:

The vagus nerve is the master switch between stress (sympathetic) and rest-digest-repair (parasympathetic) states. Gut healing requires parasympathetic dominance.

  • Cold water face splash or cold showers (activates the dive reflex)
  • Gargling vigorously with water (stimulates vagal motor fibers in the throat)
  • Humming, chanting, singing (vibrates vagal pathways)
  • Deep diaphragmatic breathing — 4-7-8 breath (inhale 4 counts, hold 7, exhale 8)
  • HRV (heart rate variability) biofeedback training

Sleep Hygiene:

Gut repair happens during deep sleep. Growth hormone peaks in the first 90 minutes of sleep, driving tissue regeneration.

  • 7-9 hours minimum
  • Consistent sleep/wake times (within 30 minutes, even on weekends)
  • Dark, cool room (65-68 degrees F)
  • No screens 60-90 minutes before bed
  • Magnesium glycinate 300-400mg before bed (supports both sleep and bowel regularity)

Mindful Eating:

  • Eat in a calm state. No eating while stressed, driving, or scrolling
  • Chew each bite 20-30 times — mechanical digestion is often overlooked
  • Cephalic phase: look at and smell your food before eating. This initiates vagal stimulation of acid and enzyme secretion before the first bite.

HPA Axis Support:

Chronic stress dysregulates the hypothalamic-pituitary-adrenal axis, raising cortisol, which directly increases intestinal permeability and shifts the microbiome toward dysbiosis.

  • Ashwagandha (KSM-66) 300-600mg/day — adaptogen that modulates cortisol
  • Phosphatidylserine 100-300mg at bedtime — blunts cortisol spike
  • Rhodiola rosea 200-400mg in the morning — supports stress resilience without stimulation

Testing and Timeline

GI-MAP (Before and After)

The GI-MAP (Microbial Assay Plus) uses quantitative PCR to measure:

  • Pathogenic bacteria (H. pylori, C. difficile, pathogenic E. coli)
  • Opportunistic bacteria (Klebsiella, Citrobacter, Pseudomonas)
  • Parasites (Blastocystis, Giardia, Cryptosporidium, worms)
  • Fungi/yeast (Candida species, Geotrichum)
  • Viral markers
  • Digestive function markers (elastase, steatocrit)
  • Inflammatory markers (calprotectin, lactoferrin, SIgA)
  • Immune markers (anti-gliadin IgA)
  • Zonulin (intestinal permeability marker)

Run a baseline GI-MAP before starting the protocol. Retest at 3-4 months to assess progress. Adjust the protocol based on results.

Typical Timeline

PhaseDurationKey Actions
REMOVEWeeks 1-6Elimination diet + antimicrobials + biofilm disruptors
REPLACEWeeks 1-6HCl, enzymes, bile — concurrent with Remove
REINOCULATEWeeks 4-12Probiotics, prebiotics, fermented foods
REPAIRWeeks 4-16Mucosal support nutrients
REBALANCEOngoingLifestyle, stress, sleep, nervous system regulation

Total protocol duration: 3-6 months minimum. Some patients with severe dysbiosis, autoimmune conditions, or longstanding damage may require 6-12 months.

The phases overlap. You do not wait until one is fully complete before starting the next. By week 4, you are typically running Phases 1-4 simultaneously, with Phase 5 woven throughout from day one.


The Deeper Teaching

In Ayurveda, they say that all disease begins in the gut — “agni” (digestive fire) is the root of health. In traditional Chinese medicine, the Spleen and Stomach are the “middle burner,” the foundation of qi production. Modern science confirms what these traditions knew for millennia: the gut is the seat of immunity, the factory of neurotransmitters, and the gatekeeper between self and non-self.

Healing the gut is not just about fixing digestion. It is about restoring the boundary between you and the world — learning what to let in, what to keep out, and how to transform what you receive into nourishment. That is a biological process. It is also a spiritual one.

The 5R Protocol is a map. Walk it with patience, precision, and respect for the intelligence of the body that is doing the actual healing. You are not fixing the gut. You are creating the conditions for the gut to fix itself.