🔬 Gluten Sensitivity Non-Celiac Gut Barrier Simulator

Gluten Ingestion & Gliadin Release

Wheat gluten breaks into gliadin fragments inside the gut lumen.

• 33-mer: Gliadin peptide (resists digestion)
• High: Digestion resistance (proline-rich sequence)
• <30 min: Reaches epithelium (after chewing)
• 0.5–13%: NCGS prevalence (of general population)

Gluten structure

Gliadin and glutenin form gluten's elastic network.

Incomplete digestion

Human enzymes cannot fully break proline-rich gliadin.

Zonulin Release From Intestinal Cells

Gliadin binds CXCR3 receptors, triggering zonulin in susceptible guts.

• CXCR3: Trigger receptor (gliadin binding site)
• Minutes: Response time (after gliadin contact)
• Subset: Responders (not all individuals react)
• Modulator: Zonulin role (tight junction assembly)

Receptor binding

Gliadin binds CXCR3 on epithelial cell surfaces.

Zonulin signal

Bound receptors trigger intracellular zonulin release.

Tight Junctions Loosen Temporarily

Zonulin disassembles junction proteins, widening gaps between cells.

• Claudin/occludin: Protein affected (junction complex)
• Transient: Permeability change (hours, not days)
• Reversible: Gap widening (reseals after exposure)
• Larger: Molecules crossing (peptides and antigens pass)

Junction disassembly

Claudin and occludin proteins pull apart.

Paracellular leak

Larger molecules pass between, not through, cells.

Bloating, Discomfort & Fatigue

Leaked antigens trigger local immune signals causing gut symptoms.

• Bloating: Common symptom (plus fatigue, discomfort)
• Hours: Onset (after exposure)
• Innate immune: Mechanism (not autoimmune)
• None: Villous damage (unlike celiac disease)

Local immune response

Innate immune cells release inflammatory signals.

Symptom pattern

Bloating, fatigue, and discomfort follow, then fade.

Distinct From Celiac Disease

Barrier changes resolve without autoantibodies or villous atrophy.

• Absent: Autoantibodies (no anti-tTG or anti-EMA)
• 0%: Villous atrophy (structure stays intact)
• Not required: HLA-DQ2/DQ8 (unlike celiac genetics)
• Full: Recovery (barrier reseals completely)

No autoimmunity

Non-celiac sensitivity lacks autoantibody production.

Villi remain intact

No flattening or crypt hyperplasia occurs.