Small Intestinal Bacterial Overgrowth (SIBO): A Comprehensive Protocol

SIBO is one of the most underdiagnosed and mismanaged conditions in gastroenterology. It is a condition where bacteria that normally reside in the large intestine migrate upstream into the small intestine, where they do not belong in significant numbers. These displaced bacteria ferment carbohydrates in the small bowel, producing gases that cause bloating, distension, pain, and altered bowel habits. But SIBO is far more than a digestive nuisance. It drives nutrient malabsorption, systemic inflammation, leaky gut, histamine overload, and has been linked to conditions as varied as rosacea, fibromyalgia, restless leg syndrome, interstitial cystitis, and hypothyroidism.

The failure rate in SIBO treatment is high — not because the antimicrobials do not work, but because clinicians kill the bacteria without addressing why they overgrew in the first place. SIBO is almost always a secondary condition. The bacteria are the symptom. The broken motility, the structural issue, the immune dysfunction — that is the disease.

---

Types of SIBO

SIBO is classified by the gases produced by the overgrown organisms. Each type presents differently and requires a distinct treatment approach.

Hydrogen-Dominant SIBO

The most common type. Bacteria ferment carbohydrates and produce hydrogen gas. This type typically presents with:

• Diarrhea or loose stools
• Bloating, especially after meals
• Urgency
• Flatulence
• Abdominal cramping

Hydrogen-producing organisms include various species of Streptococcus, E. coli, Klebsiella, and other gram-negative bacteria.

Methane-Dominant SIBO (Intestinal Methanogen Overgrowth — IMO)

Now more accurately called IMO because the methane producers (archaea, primarily Methanobrevibacter smithii) are not bacteria. They are a separate domain of life. These organisms consume hydrogen produced by other bacteria and convert it to methane. Methane slows gut transit — it literally paralyzes the smooth muscle of the intestine.

Presentation:

• Constipation (often severe, sometimes only 1-2 bowel movements per week)
• Bloating and distension
• Hard, dry stools
• Straining
• Feeling of incomplete evacuation
• Weight gain (methane producers increase caloric extraction from food)

IMO is harder to eradicate than hydrogen SIBO and has a higher relapse rate.

Hydrogen Sulfide SIBO

The newest recognized type. Organisms like Desulfovibrio and Bilophila wadsworthensis reduce sulfate to hydrogen sulfide gas. Until 2020, standard breath tests could not detect this gas. The trio-smart breath test now measures all three gases.

Presentation:

• Diarrhea (often sulfur-smelling, “rotten egg” gas)
• Bladder pain, urgency
• Sensitivity to sulfur-containing foods (garlic, onions, cruciferous vegetables, eggs, wine)
• Brain fog
• Visceral hypersensitivity

---

Testing for SIBO

Lactulose Breath Test

The standard test. The patient drinks a lactulose solution (a non-absorbable sugar) after a 12-hour fast and a 24-hour preparatory diet (white rice, plain chicken, eggs, clear broth — no fiber, no fermentable foods). Breath samples are collected every 15-20 minutes for 3 hours, measuring hydrogen, methane, and (with trio-smart) hydrogen sulfide.

Interpretation:

• Hydrogen: A rise of 20+ ppm above baseline within the first 90 minutes suggests small intestinal bacterial overgrowth (before the lactulose reaches the cecum)
• Methane: Levels of 10+ ppm at any point during the test are considered positive for IMO
• Hydrogen sulfide: Levels above 3 ppm are considered positive

Limitations: The lactulose breath test has a sensitivity of approximately 52-68% and specificity of 44-86%. False negatives are common. A negative breath test does not definitively rule out SIBO, especially hydrogen sulfide type.

Glucose Breath Test

More specific but less sensitive than lactulose. Glucose is absorbed in the proximal small intestine, so it only detects overgrowth in the upper portion. It will miss distal small intestinal overgrowth. Rise of 12+ ppm hydrogen above baseline within 90 minutes is positive.

Timing Considerations

• 24-hour prep diet before the test (low residue)
• 12-hour overnight fast
• No antibiotics or herbal antimicrobials for at least 2 weeks prior (4 weeks preferred)
• No probiotics for 1 week prior
• No prokinetics for 3 days prior
• No laxatives for 1 week prior
• Test first thing in the morning

---

Root Causes: Why Bacteria Overgrow

This is where most practitioners fail. They treat the overgrowth and never ask why it happened. SIBO recurrence rates reach 40-50% within a year if root causes are not addressed.

Impaired Motility (The #1 Cause)

The migrating motor complex (MMC) is a cyclical wave of muscular contraction that sweeps through the small intestine approximately every 90-120 minutes during fasting. It is the intestinal housekeeper — clearing debris, bacteria, and undigested food particles, pushing them downstream toward the colon. When the MMC is impaired, bacteria accumulate.

The MMC only activates in a fasting state. Every time you eat, the MMC shuts off. This is why meal spacing is critical: 4-5 hours between meals with no snacking. Every snack, every handful of nuts, every splash of cream in your coffee between meals interrupts the cleaning wave.

Post-Infectious SIBO (The Food Poisoning Connection)

Mark Pimentel’s groundbreaking research at Cedars-Sinai demonstrated that acute food poisoning (Salmonella, Campylobacter, E. coli, Shigella) can trigger an autoimmune response against the body’s own nerve cells in the gut. The pathogen produces cytolethal distending toxin B (CdtB). The immune system produces antibodies against CdtB, but these antibodies cross-react with vinculin, a protein essential for the function of the interstitial cells of Cajal — the pacemaker cells that drive the MMC.

The result: permanent or semi-permanent damage to gut motility, leading to chronic SIBO. The IBS Smart test measures anti-CdtB and anti-vinculin antibodies and can confirm this mechanism.

Other Root Causes

• Low stomach acid — acid kills bacteria before they reach the small intestine. PPIs (proton pump inhibitors) increase SIBO risk by 2-8x.
• Ileocecal valve dysfunction — this valve separates the small and large intestine. If it is incompetent, colonic bacteria reflux upward into the small bowel. Manual visceral manipulation by an osteopath or skilled bodyworker can help.
• Adhesions — from surgery, endometriosis, Crohn’s disease, or pelvic inflammatory disease. Physical scar tissue creates mechanical obstruction and pockets where bacteria accumulate. Clear Passage Physical Therapy (Wurn technique) specializes in non-surgical adhesion release.
• Hypothyroidism — slows gut motility. Always check TSH, free T3, free T4, and thyroid antibodies in SIBO patients.
• Diabetes — diabetic neuropathy affects the enteric nervous system, impairing motility.
• Medications — PPIs, opioids, anticholinergics, tricyclic antidepressants all slow motility or reduce gastric acid.
• Ehlers-Danlos syndrome — connective tissue laxity affects gut structure and motility. SIBO prevalence in EDS is extremely high.
• Structural issues — diverticula, strictures, blind loops from surgery

---

Treatment Protocols

Herbal Antimicrobial Protocol

A landmark study by Johns Hopkins (Chedid et al., 2014) found herbal antimicrobials were as effective as Rifaximin for SIBO eradication, with fewer side effects.

For Hydrogen-Dominant SIBO:

• Allicin (stabilized garlic extract) 450mg 2x/day — Allimed or Allimax brand. Active against a wide range of gram-positive and gram-negative bacteria.
• Berberine (from goldenseal, Oregon grape, or barberry) 500mg 2-3x/day — broad-spectrum antimicrobial, also modulates blood sugar and bile flow
• Oregano oil (standardized to 60-75% carvacrol) 200mg 2x/day — potent against gram-negative organisms
• Neem 300-500mg 2x/day — traditional Ayurvedic antimicrobial, particularly effective against gram-negative bacteria and biofilms

Run for 4-6 weeks. Some practitioners use two sequential 4-week rounds with different combinations to prevent resistance.

For Methane-Dominant / IMO:

Methanogens are archaea — they are not killed by standard antibiotics or most herbal antimicrobials. You need specific agents:

• Allicin 450mg 2-3x/day (higher dose for methane) — the single most effective natural agent against methanogens
• Berberine 500mg 3x/day
• Oregano oil 200mg 2-3x/day
• Atrantil — a blend of quebracho, horse chestnut, and peppermint specifically designed for methane/hydrogen sulfide SIBO. 2 capsules 3x/day with meals during treatment phase, then 2 capsules daily for maintenance.

For Hydrogen Sulfide:

• Bismuth (Pepto-Bismol) 524mg 4x/day — bismuth binds hydrogen sulfide. This is one of the few situations where an OTC medication is a frontline functional medicine recommendation.
• Oregano oil
• Uva ursi
• Low-sulfur diet during treatment (limit garlic, onions, cruciferous vegetables, eggs, wine)
• Molybdenum 500mcg/day — cofactor for sulfite oxidase, helps process sulfur compounds

Pharmaceutical Protocol

• Rifaximin 550mg 3x/day for 14 days — a non-absorbed antibiotic that stays in the gut. Approximately 50% effective for hydrogen SIBO after one course.
• For methane/IMO: Rifaximin 550mg 3x/day + Neomycin 500mg 2x/day for 14 days. The combination targets both bacteria (hydrogen producers) and archaea (methane producers).
• For hydrogen sulfide: Rifaximin + Bismuth subsalicylate

Some practitioners use a “weed and feed” approach: taking a small amount of prebiotic (like PHGG 5g/day) during Rifaximin treatment. The theory is that metabolically active bacteria are more susceptible to antibiotics than dormant ones. Pimentel’s research supports this strategy.

Elemental Diet

The nuclear option. An elemental diet is a pre-digested liquid formula containing amino acids, simple sugars, and fats that are fully absorbed in the first few feet of the small intestine. Nothing reaches the bacteria further downstream. They starve.

• Duration: 2-3 weeks (minimum 14 days)
• Efficacy: 80-85% effective for SIBO eradication by breath test (Pimentel et al., 2004)
• Products: Physicians’ Elemental Diet (Integrative Therapeutics), Absorb Plus, or homemade formulas
• Caloric target: typically 1,500-2,000 calories/day from the formula
• Nothing else by mouth except water, herbal tea, and prescribed medications

This is challenging. Two to three weeks consuming only a sweet liquid formula tests willpower. But for recalcitrant SIBO — cases that have failed multiple rounds of antimicrobials — it can be transformative.

---

Prokinetics: The Most Critical Step

After eradication, you MUST support the migrating motor complex. Without prokinetics, relapse is nearly inevitable.

Prescription Prokinetics:

• Low-dose erythromycin 50mg at bedtime — at this sub-antimicrobial dose, erythromycin acts as a motilin receptor agonist, directly stimulating the MMC. This is Pimentel’s preferred prokinetic.
• Low-dose naltrexone (LDN) 2.5-4.5mg at bedtime — modulates endorphin and immune function, improves motility, reduces visceral hypersensitivity. Compounding pharmacy required. Has additional benefits for autoimmune conditions.
• Prucalopride 1-2mg daily — 5-HT4 receptor agonist. Strongest evidence for constipation-predominant cases (IMO).

Natural Prokinetics:

• Ginger — Prokinetic dose is 1,000mg/day of a concentrated extract (not tea). Stimulates antral contractions and accelerates gastric emptying.
• MotilPro (Pure Encapsulations) — contains 5-HTP (serotonin precursor, and 90% of serotonin is in the gut) plus ginger. 2 capsules at bedtime.
• Iberogast — a nine-herb European formula (STW 5) with strong clinical evidence for functional dyspepsia and IBS. 20 drops 3x/day before meals. Contains iberis amara, chamomile, peppermint, caraway, licorice, lemon balm, angelica, celandine, and milk thistle.

Prokinetic protocol: Start after antimicrobial treatment is complete. Continue for a minimum of 3 months. Some patients — especially those with post-infectious SIBO and elevated anti-vinculin antibodies — may need prokinetics indefinitely.

---

SIBO-Specific Diets

Low-FODMAP Diet

The most researched diet for IBS/SIBO symptom management. Reduces fermentable substrates: Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols. Effective for symptom control but not curative. Not meant to be followed long-term (restricts prebiotic fiber that feeds beneficial bacteria).

Bi-Phasic Diet (Dr. Nirala Jacobi)

Specifically designed for SIBO. Two phases:

• Phase 1 (Restrictive, 4-6 weeks): During antimicrobial treatment. Very low fermentation potential. Removes grains, most legumes, dairy, sugar, and high-FODMAP vegetables.
• Phase 2 (Reintroduction): Gradually expands food variety as bacterial load decreases. Systematically tests tolerance.

Specific Carbohydrate Diet (SCD)

Developed by Dr. Sidney Haas, popularized by Elaine Gottschall. Removes all disaccharides and polysaccharides (grains, starch, most sugars except honey). Allows monosaccharides only. Can be effective but is very restrictive.

Key dietary principle across all approaches: Meal spacing of 4-5 hours between meals with NO snacking to allow the MMC to activate. This single behavioral change is more important than any specific diet.

---

Biofilm Disruption

Persistent SIBO often involves biofilm-protected communities. Add biofilm disruptors during the first 1-2 weeks of antimicrobial treatment:

• NAC 600mg 2x/day on an empty stomach
• InterFase Plus (Klaire Labs) — contains EDTA and biofilm-degrading enzymes
• Bismuth thiol compounds
• Lauricidin (monolaurin) 1-3 scoops/day
• EDTA — chelates calcium and iron in the biofilm matrix
• Phase 2 Biofilm Advanced (Priority One) — enzymes targeting polysaccharide biofilm structures

Take biofilm agents 30-60 minutes before antimicrobials on an empty stomach.

---

Prevention of Relapse — The Missing Piece

This is where the real work begins. Killing bacteria is the easy part. Keeping them from returning is the challenge.

1. Prokinetics — minimum 3 months, often 6-12 months or indefinitely. Non-negotiable.
2. Meal spacing — 4-5 hours between meals. No snacking. Water and black coffee/tea between meals are acceptable.
3. Address root causes — thyroid optimization, acid replacement, ileocecal valve work, adhesion therapy, medication review
4. Stress management — chronic stress suppresses MMC activity via sympathetic dominance
5. Post-meal walking — 10-15 minutes of gentle walking after meals improves gastric emptying and small bowel transit
6. Slow, careful food reintroduction — expand the diet gradually over 3-6 months. Permanent restriction leads to microbiome impoverishment.
7. Strategic probiotic use — S. boulardii during and after treatment. Spore-based probiotics (MegaSporeBiotic) post-treatment. Avoid high-dose Lactobacillus probiotics until SIBO is cleared (they are lactic acid bacteria and can worsen SIBO in some patients).

---

Connected Conditions

SIBO does not exist in isolation. The research connecting it to systemic conditions continues to grow:

• IBS — up to 78% of IBS patients test positive for SIBO (Pimentel et al.). SIBO may be the underlying mechanism for a majority of IBS cases.
• Rosacea — patients with rosacea have a significantly higher prevalence of SIBO. SIBO eradication leads to resolution of rosacea in many patients (Parodi et al., 2008).
• Restless Leg Syndrome (RLS) — SIBO causes systemic inflammation and impairs iron absorption. Iron deficiency in the basal ganglia is implicated in RLS. Treating SIBO can resolve RLS symptoms.
• Fibromyalgia — SIBO prevalence is elevated in fibromyalgia. The LPS (endotoxin) and cytokine burden from SIBO may drive central sensitization.
• Hypothyroidism — bidirectional relationship. Hypothyroidism slows motility causing SIBO; SIBO-driven inflammation impairs thyroid conversion (T4 to T3) and increases thyroid autoimmunity.
• Acne — the gut-skin axis. SIBO increases intestinal permeability, driving systemic inflammation that manifests on the skin.
• Interstitial cystitis — histamine overproduction from certain SIBO organisms may drive bladder inflammation.

---

A Final Reflection

SIBO teaches a fundamental lesson about the body: you cannot outsmart a system that is smarter than you. The bacteria are not the enemy. They are organisms doing what organisms do — colonizing available habitat. The question is not “how do I kill these bacteria?” but “why has my body lost the ability to keep them in their proper place?”

The MMC, stomach acid, bile flow, ileocecal valve competence, immune surveillance — these are the body’s own SIBO prevention systems. They evolved over millions of years. When we restore them, the body does what it has always known how to do: maintain order.

The antimicrobials clear the board. The prokinetics and root-cause work keep it clear. The diet feeds recovery. The nervous system regulation allows healing. All four pillars must stand together. Remove one, and the whole structure eventually falls.