What Is Celiac Disease?
Celiac disease is a chronic autoimmune disorder triggered by gluten in genetically susceptible individuals. When gluten is consumed, the immune system attacks the small intestine's villi—finger-like projections that absorb nutrients.
The Genetic Component
Almost all people with celiac disease carry one of two gene variants: HLA-DQ2 or HLA-DQ8. About 30% of the general population carries these genes, but only 2-3% of carriers develop celiac disease. This suggests additional genetic and environmental factors are involved.
The Immune Response
When someone with celiac disease eats gluten, an enzyme called tissue transglutaminase (tTG) modifies gliadin proteins. This modification creates a shape that fits perfectly into the HLA-DQ2 or DQ8 receptors on immune cells, triggering an inflammatory cascade.
The Role of Zonulin
Research by Dr. Alessio Fasano identified zonulin, a protein that regulates intestinal permeability. In celiac patients, gluten triggers excess zonulin release, increasing gut permeability ("leaky gut"). This allows gluten fragments to enter the bloodstream and trigger immune responses.
Beyond the Gut: Systemic Effects
Celiac disease affects more than just digestion:
- Dermatitis herpetiformis - intensely itchy skin rash
- Neurological symptoms - ataxia, neuropathy, brain fog
- Bone health - osteoporosis from malabsorption
- Reproductive issues - infertility, recurrent miscarriage
Diagnosis Methods
Blood Tests
Testing for tTG-IgA antibodies is the most common first step. Elevated levels suggest celiac disease but require confirmation.
Intestinal Biopsy
The gold standard for diagnosis. Samples show villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
Genetic Testing
HLA-DQ2/DQ8 testing can rule out celiac disease—if you don't have these genes, you can't develop celiac. However, having them doesn't mean you will develop it.
Current Research Directions
Enzyme Therapies
Researchers are developing enzymes that can break down gluten before it causes damage. Latiglutenase and other candidates are in clinical trials.
Tight Junction Modulators
Larazotide acetate works by preventing zonulin from opening tight junctions, potentially reducing intestinal permeability.
Gluten-Degrading Probiotics
Certain bacterial strains can break down gluten. Research is exploring probiotic supplements that could help digest accidental gluten exposure.
Immune Tolerance Approaches
Nexvax2 and similar vaccines aim to desensitize the immune system to gluten, similar to allergy immunotherapy.
The Microbiome Connection
Studies show celiac patients have distinct gut microbiome profiles. Whether this is a cause or consequence of the disease is under investigation. Research suggests early antibiotic use and cesarean birth may increase risk.
Environmental Triggers
Beyond genetics, several factors may trigger celiac disease onset:
- Viral infections (reovirus has been linked to celiac onset)
- Early introduction of gluten
- Breastfeeding duration
- Antibiotic exposure in infancy
Non-Celiac Gluten Sensitivity
NCGS remains poorly understood. Recent research suggests FODMAPs (fermentable carbohydrates) in wheat may cause some symptoms attributed to gluten sensitivity. More research is needed to understand this condition.
Conclusion
Our understanding of celiac disease has advanced significantly. While a strict gluten-free diet remains the only current treatment, research into therapies that could allow safe gluten consumption offers hope for the future. Continued research into the microbiome, genetics, and immune system may eventually lead to prevention or cure.