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TOBIN Intelligence Library · evidence review

Gut Dysbiosis & SIBO

Dysbiosis means an unhealthy change in gut microbes. It is a research concept, and there is no validated lab test for it. Stool microbiome panels are not recommended for diagnosis. The parts that can be measured are small-intestinal bacterial overgrowth (SIBO) and gut inflammation. SIBO is shown by a lactulose or glucose breath test with a hydrogen rise of 20 ppm or more within 90 minutes, or methane of 10 ppm or more (North American Consensus 2017). Gut inflammation is shown by fecal calprotectin above about 50 µg/g, which calls for workup to exclude inflammatory bowel disease.

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What is well established

1 links
  • Antibiotics, low-fiber diet → Loss of microbial diversityB

    Fiber feeding trials raise short-chain-fatty-acid producers; antibiotics reduce diversity for months.

    Randomized evidence · Moderate clinical evidence

What is suspected, not proven

3 links
  • Reduced gut motility (diabetes, opioids, hypothyroidism) → SIBOB

    Impaired migrating motor complex lets bacteria accumulate in the small bowel.

    Open question: the association may reflect confounding or reverse causation; intervention trials would settle it.

  • Dysbiosis → Systemic low-grade inflammationC

    Endotoxin translocation raises inflammatory signalling; human causation remains unproven.

    Open question: the mechanism is shown in cells or animals; human outcome trials are still needed.

  • SIBO → Bloating, B12 and iron malabsorptionB

    Bacterial consumption of B12 and mucosal injury.

    Open question: the association may reflect confounding or reverse causation; intervention trials would settle it.

iDetection of an exposure does not establish that it caused a disease. This platform separates exposure, association, plausible mechanism, clinical evidence and demonstrated causation.

Domain emphasis

I Inflammation & Infection · 1N Nutrition · 0.9T Toxins · 0.6O Oxidative Stress · 0.5B Hormonal Balance · 0.5

Bacteria are the subject here. Treat SIBO only when a breath test is positive. Probiotics and FMT are proven only for specific indications, such as recurrent C. difficile.

Related Quadpandemics

  • II · Obesity & Metabolic Dysfunction

    Obesity is a signaling and exposure problem, not a number on a scale.

  • III · Allergy & Immune Dysregulation

    Allergic and immune-complex disease is the fastest-rising chronic burden of the century.

  • IV · Anxiety, Depression & Neurobehavioral Health

    Mood symptoms are assessed responsibly — never automatically attributed to toxins or hormones.

Labs that inform this review

  • hs-CRP (< 1.0 mg/L) — Non-specific inflammatory burden. Values above 10 mg/L usually indicate an acute process needing evaluation.
  • 25-OH vitamin D (30–60 ng/mL) — Nutrient status relevant to immune and musculoskeletal function. Severe deficiency with bone pain or falls needs clinical review.
  • Ferritin (30–300 ng/mL) — Iron stores, but also an acute-phase reactant. Iron deficiency in adults needs a source investigation.
  • Anti-TPO antibodies (< 35 (assay-specific) IU/mL) — Thyroid peroxidase antibodies — the main marker of autoimmune (Hashimoto's) thyroiditis. Positive antibodies in pregnancy or with rising TSH deserve clinician follow-up.
  • Thyroglobulin antibodies (≤ 4 (assay-specific) IU/mL) — Second autoimmune thyroid marker; occasionally positive when anti-TPO is negative. Review with a clinician alongside TSH and free T4.
  • Lp-PLA2 activity (≤ 123 nmol/min/mL) — Vascular-specific inflammatory enzyme (PLAC test, FDA-cleared). Review with a clinician as part of cardiovascular risk.

Score cutoffs used

  • hs-CRP AHA/CDC: <1 lower, 1–3 average, >3 higher cardiovascular-inflammatory risk; >10 suggests acute process
  • 25-OH vitamin D Endocrine Society: <20 ng/mL deficient, 20–29 insufficient; IOM <12 deficient
  • Ferritin AGA 2020: ferritin <45 ng/mL supports iron deficiency; WHO <15 depleted
  • Vitamin B12 <200 pg/mL deficient; 200–300 borderline (confirm with MMA)
  • Magnesium (serum) Serum reference ≈ 1.7–2.2 mg/dL; serum underestimates total body stores
  • Omega-3 index Harris & von Schacky: >8% desirable, <4% undesirable
  • Homocysteine >15 µmol/L elevated in most laboratory references
  • Eosinophils (absolute) >500 cells/µL eosinophilia; ≥1500 hypereosinophilia
  • Total IgE Adult reference typically <100 IU/mL; context-dependent
  • White blood cells Reference ≈ 4.0–11.0 ×10³/µL
  • Free T3 Typical reference 2.3–4.2 pg/mL; low T3 also occurs in illness and calorie restriction
  • Anti-TPO antibodies Common cutoff >34–35 IU/mL (assay-specific); marks Hashimoto's risk (ATA)
  • Thyroglobulin antibodies Common cutoff ≤4 IU/mL (Roche) — assay-specific; positive in ~60–80% of Hashimoto's
  • Lp-PLA2 activity PLAC Activity test (FDA-cleared): >123 nmol/min/mL higher risk

Key formulas and thresholds

Published clinical cutoffs
  • HOMA-IR = fasting glucose (mg/dL) × fasting insulin (µIU/mL) ÷ 405 — above 2.5 suggests insulin resistance (Matthews 1985).
  • BMI = weight (kg) ÷ height (m)² — 25–29.9 overweight, 30 or more obesity (WHO); lower cutoffs (23/27.5) for many Asian populations.
  • Waist-to-height ratio = waist ÷ height — 0.5 or more signals central adiposity (NICE 2022).
  • TG/HDL ratio = triglycerides ÷ HDL (mg/dL) — above 3 is associated with insulin resistance (observational).
  • hs-CRP (mg/L): concern above 1, scored 100 at 10 — AHA/CDC: <1 lower, 1–3 average, >3 higher cardiovascular-inflammatory risk; >10 suggests acute process
  • 25-OH vitamin D (ng/mL): concern below 30, scored 100 at 5 — Endocrine Society: <20 ng/mL deficient, 20–29 insufficient; IOM <12 deficient
  • Ferritin (ng/mL): concern below 30, scored 100 at 5; concern above 300, scored 100 at 1000 — AGA 2020: ferritin <45 ng/mL supports iron deficiency; WHO <15 depleted
  • Vitamin B12 (pg/mL): concern below 300, scored 100 at 100 — <200 pg/mL deficient; 200–300 borderline (confirm with MMA)
  • Magnesium (serum) (mg/dL): concern below 1.8, scored 100 at 1.2 — Serum reference ≈ 1.7–2.2 mg/dL; serum underestimates total body stores
  • Omega-3 index (%): concern below 8, scored 100 at 3 — Harris & von Schacky: >8% desirable, <4% undesirable
  • Homocysteine (µmol/L): concern above 10, scored 100 at 30 — >15 µmol/L elevated in most laboratory references
  • Eosinophils (absolute) (cells/µL): concern above 500, scored 100 at 3000 — >500 cells/µL eosinophilia; ≥1500 hypereosinophilia
  • Total IgE (IU/mL): concern above 100, scored 100 at 1000 — Adult reference typically <100 IU/mL; context-dependent
  • White blood cells (×10³/µL): concern above 11, scored 100 at 20 — Reference ≈ 4.0–11.0 ×10³/µL
  • Free T3 (pg/mL): concern below 2.5, scored 100 at 1.8; concern above 4.4, scored 100 at 7 — Typical reference 2.3–4.2 pg/mL; low T3 also occurs in illness and calorie restriction
  • Anti-TPO antibodies (IU/mL): concern above 34, scored 100 at 500 — Common cutoff >34–35 IU/mL (assay-specific); marks Hashimoto's risk (ATA)
  • Thyroglobulin antibodies (IU/mL): concern above 4, scored 100 at 200 — Common cutoff ≤4 IU/mL (Roche) — assay-specific; positive in ~60–80% of Hashimoto's
  • Lp-PLA2 activity (nmol/min/mL): concern above 123, scored 100 at 225 — PLAC Activity test (FDA-cleared): >123 nmol/min/mL higher risk

iThese thresholds organize where to look; they do not diagnose. Laboratory ranges, age, sex and pregnancy change interpretation.

Published sources

Guidelines and landmark studies
Protocols for Gut Dysbiosis & SIBOCalculate my TOBIN scoresAll reviews