TOBIN Intelligence Library · evidence review
IBS & Gut Barrier Dysfunction
Symptoms are mapped across diet, motility, visceral sensitivity, microbial ecology, immune activation and exposures, while red flags are routed to conventional evaluation first.
What is well established
2 links- Fermentable carbohydrate load → Bloating and painA
Low-FODMAP trials demonstrate symptom reduction in a substantial subgroup.
Randomized evidence · Multiple high-quality guidelines or meta-analyses
- Stress and autonomic load → Symptom amplificationB
Gut-directed hypnotherapy and CBT reduce symptom severity in trials.
Randomized evidence · Moderate clinical evidence
What is suspected, not proven
2 links- Post-infectious immune activation → Visceral hypersensitivityB
Post-infectious IBS cohorts show persistent mucosal immune changes and altered sensation.
Open question: the association may reflect confounding or reverse causation; intervention trials would settle it.
- Bacteriome and bile-acid alteration → Stool-form changeC
Bile-acid malabsorption and microbial shifts plausibly affect transit; testing is often inconclusive.
Open question: the mechanism is shown in cells or animals; human outcome trials are still needed.
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
Core Fifth Estate case: a stool organism report is classified as active infection, colonization, dysbiosis hypothesis, past exposure or incidental detection before any antimicrobial is discussed.
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.