What causes recurrent SIBO?

The Host Capacity Model identifies colonocyte bioenergetic failure as the upstream driver of recurrent SIBO. When colonocyte mitochondrial respiration fails, oxygen leaks into the lumen and reshapes the ecology toward facultative and sulfidogenic overgrowth—so antimicrobials clear the symptom but not the cause.

How is MCAS different from other mast cell conditions?

BiomeLogic stratifies MCAS into Pattern A/B/C/D activation phenotypes based on upstream drivers (barrier, neuroimmune, infectious, or connective-tissue mediated). Treatment differs by pattern, which is why generic mast-cell stabilizers fail in many patients.

Do you provide medical care or diagnoses?

No. BiomeLogic provides independent systems-biology consultation and mechanistic case analysis. It is not medical care, not a diagnosis, and does not replace your physician.

Can probiotics cure dysbiosis?

Not alone. Probiotics are supportive, not curative. They work when host capacity is intact or recovering, dysbiotic species have been suppressed, the barrier is healing, and the diet supports beneficial bacteria. They fail when colonocyte bioenergetics are still depleted or when introduced before antimicrobial suppression.

Why don't probiotics fix dysbiosis on their own?

Probiotics introduce beneficial bacteria but cannot restore colonocyte mitochondrial function, repair tight junctions, or reverse NAD+ depletion. Without host-side restoration, beneficial bacteria can't establish — the ecological niche that supports them is missing.

What causes treatment-refractory dysbiosis?

Persistent colonocyte bioenergetic failure. As long as NAD+ is depleted and mitochondrial function is impaired, the gut barrier remains compromised and dysbiotic species keep the ecological advantage. Refractory dysbiosis is almost always a Host Capacity problem, not a bacterial-resistance problem.

How does the Host Capacity Model reframe dysbiosis?

Standard models treat dysbiotic bacteria as the disease. The Host Capacity Model treats dysbiosis as the symptom of an upstream colonocyte energy crisis. Restore the host — NAD+, butyrate, barrier, mitochondrial cofactors — and dysbiosis resolves because the ecological pressure that selected for it is gone.

Can the gut barrier be restored?

Yes, but only when colonocyte bioenergetics recover. Tight junction proteins (claudins, ZO-1) are ATP-dependent. NAD+ restoration, butyrate support, L-glutamine, zinc carnosine, and bone broth all contribute, but the upstream energy crisis must be addressed first or barrier repair stalls.

How long does dysbiosis recovery take?

Antimicrobial phase: 4–6 weeks. Dietary restriction: 6–8 weeks. Bioenergetic recovery: 12–24 weeks. Sustainable maintenance: 6–12 months. Most patients see major symptom improvement by week 8–12 if the protocol addresses host capacity, not just bacterial load.

Condition framework

Treatment-Refractory Dysbiosis: Why Probiotics Failed

Why standard dysbiosis protocols fail in chronic cases, and how the Host Capacity Model and ecological thermodynamics reframe restoration of the gut microbiome.

What is dysbiosis — and why conventional treatment fails

Dysbiosis is an alteration in the microbial community: ↓ beneficial bacteria (Faecalibacterium, Roseburia, Akkermansia), ↑ pathogenic bacteria (Klebsiella, Citrobacter, Desulfovibrio), loss of microbial diversity, altered metabolite production (↓ butyrate, ↑ secondary bile acids, ↑ LPS), and increased intestinal permeability.

Standard treatment kills bacteria with antibiotics, herbals, or restrictive diet. But it doesn't address why bacteria overgrew in the first place. Dysbiosis recurs because the host capacity — the colonocyte's ability to maintain a healthy environment — never recovered.

The Host Capacity Model: dysbiotic bacteria are secondary. The primary lesion is colonocyte bioenergetic failure. Restore the host, and dysbiosis resolves.

The cascade: how dysbiosis develops

Step 1: Colonocyte bioenergetic crisis. Colonocytes depend on mitochondrial ATP for tight junctions, mucus secretion, antimicrobial peptide synthesis, and barrier function. When mitochondrial function fails — from CD38-driven NAD+ depletion, Complex I/II impairment, SIRT3 loss, Fe-S cluster failure — colonocytes can no longer maintain the environment.

Step 2: Barrier collapse. Tight junctions break down, the mucus layer thins, antimicrobial defenses decline, permeability increases. Dysbiotic species preferentially exploit this — fast-growing gram-negatives (Klebsiella, Citrobacter), H₂S-producers (Desulfovibrio), methanogens (Methanobrevibacter smithii).

Step 3: Dysbiotic metabolites. ↓ Butyrate (Faecalibacterium, Roseburia loss). ↑ Secondary bile acids. ↑ H₂S. ↑ D-lactate. ↑ LPS. ↑ Uremia from dysbiotic proteolysis.

Step 4: Endotoxemia loop. LPS translocation triggers IL-6, TNF-α, IL-1β production via TLR4. This perpetuates CD38 upregulation and consumes more NAD+, closing the loop. Dysbiosis perpetuates the very bioenergetic failure that created it.

Phase 1: Bioenergetic assessment

Identify the specific energy bottleneck driving dysbiosis. Panel: Organic Acid Test; intracellular NAD+ panel; mitochondrial markers (lactate, carnitine, CoQ10); Fe-S cluster proxies (iron, B2, B3); inflammation and barrier (hs-CRP, LPS/LBP, zonulin, calprotectin). If NAD+ is depleted and inflammation is high, prioritize anti-inflammatory and NAD+ restoration.

Phase 2: Dysbiotic ecosystem mapping

Shotgun metagenomics for full species and functional gene profile. Quantitative SCFA panel for butyrate production. Barrier markers — zonulin, calprotectin, LPS/LBP. Interpretation: high Klebsiella + low Faecalibacterium + low butyrate = advanced gram-negative dysbiosis. High Desulfovibrio + neurological symptoms = H₂S-driven dysbiosis. High calprotectin + high zonulin = active dysbiosis-driven inflammation.

Phase 3: Dysbiosis restoration protocol (8–16 weeks)

Antimicrobial phase (weeks 1–6). Botanicals first: allicin extract 450 mg three times daily; berberine 500 mg twice daily; oil of oregano 75–150 mg three times daily; bismuth subnitrate 240 mg twice daily. If inadequate (weeks 5–6): rifaximin 550 mg twice daily for 14 days. For Desulfovibrio dominance: add molybdenum cofactor (75–150 mcg), zinc carnosine (150 mg twice daily), reduced L-glutathione (500–1000 mg).

Dietary phase (weeks 1–8). Low-FODMAP framework starves dysbiotic fermentation. Bloating after a food signals dysbiotic recurrence. Emphasize bioenergetic substrates: MCT oil 1–2 tablespoons daily; polyphenols (berries, green tea, dark chocolate); high-quality amino acids (grass-fed meat, wild fish, bone broth); small frequent protein feeds. Weeks 6–8: slow reintroduction toward Mediterranean-style.

Host restoration (weeks 1–12+). NMN 500–1000 mg daily (preferred), NR 500–1000 mg daily, or IV NAD+ 250–500 mg weekly for 4–8 weeks if severely depleted — target intracellular NAD+ >500 μM by week 8. Sodium butyrate (enteric-coated) 1–2 g daily for 8–12 weeks. After week 8, prebiotics: inulin 5–15 g daily. Mitochondrial cofactors: ubiquinol 200–400 mg, B2 100–200 mg, B3 50–100 mg, L-carnitine 500–2000 mg, iron only if ferritin <50 and inflammatory markers low. Mucosal healing: L-glutamine 5–10 g, zinc carnosine 150–300 mg, bone broth 8–12 oz, slippery elm 1–2 g daily.

Phase 4: Prevention and long-term maintenance

Retest at week 12: intracellular NAD+ >500 μM, metagenomics showing ↑ Faecalibacterium and ↓ dysbiotic gram-negatives, barrier markers (↓ zonulin, ↓ calprotectin). Discontinue antimicrobials, begin FODMAP reintroduction, transition butyrate from pharmaceutical to food-based (resistant starch, whole grains). Continue NAD+ support indefinitely (~500 mg daily). Now introduce a multi-strain clinical-grade probiotic, starting low.

Maintenance: NMN 500 mg, resistant starch or inulin 10–20 g, polyphenol-rich foods, daily probiotics, bone broth or collagen hydrolysate. Weekly 16–18 hour intermittent fasting to support autophagy. Stress management to maintain parasympathetic tone. Reassess monthly; if recurrence signals start, return to Phase 3 for 4 weeks.

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