Is it Coeliac Disease or Gluten Intolerance?

In many cases of auto-immune conditions such as psoriasis and lichen sclerosis, it is recommended to avoid gluten due to its inflammatory effect on the system. This does not mean that you have coeliac disease and are allergic to gluten, but what is the difference.

Coeliac disease: an autoimmune condition

Coeliac disease isn't a food intolerance at all — it's an autoimmune disease triggered by gluten.

What happens:

1. The trigger: Gluten contains a protein fraction called gliadin, which is unusually resistant to being fully broken down by digestive enzymes. Fragments of it survive digestion intact.

2. Crossing the barrier: In someone with coeliac disease, these gliadin fragments cross the gut lining (either through it or between the cells) into the deeper tissue of the small intestine.

3. The immune trigger: An enzyme called tissue transglutaminase (tTG) modifies the gliadin fragments in a process called deamidation. This changes their shape in a way that makes them bind very effectively to specific immune receptors (HLA-DQ2 or HLA-DQ8) on antigen-presenting cells. This is why coeliac disease has a strong genetic component — you need one of these HLA variants to develop it (though having the gene isn't enough on its own).

4. The immune attack: Once presented, these modified gliadin fragments activate helper T-cells, which trigger a cascade — inflammatory cytokine release, activation of B-cells producing antibodies (including anti-tTG antibodies, which is what coeliac blood tests look for), and recruitment of cytotoxic T-cells into the gut lining itself.

5. The damage: This immune assault damages the villi — the finger-like projections lining the small intestine that absorb nutrients. Over time this causes villous atrophy (flattening of the villi) and crypt hyperplasia. Flattened villi mean drastically reduced surface area for absorption, leading to malabsorption of iron, B12, folate, fat-soluble vitamins, calcium, etc.

Even trace gluten exposure can trigger it, and the immune response can continue causing damage for a while after exposure, even without symptoms every time.

Non-coeliac gluten sensitivity (NCGS): is not autoimmune and not fully understood

This is the "gluten intolerance" most people mean when they use that phrase, and it's mechanistically quite different,

What's thought to happen:

• No villous atrophy or damage, no anti-tTG antibodies, negative coeliac genetic markers in most cases — the small intestine structure stays essentially normal.

• The leading theories involve:

  • Innate immune activation (not the adaptive/autoimmune response seen in coeliac) — some studies show increased markers of innate immune activity in the gut.

  • Increased intestinal permeability ("leaky gut") allowing more gut contents to interact with immune tissue, provoking a low-grade inflammatory response without the full autoimmune cascade.

  • FODMAPs, not gluten: A significant body of research suggests that in many people diagnosed with NCGS, the actual culprit may be FODMAPs (fermentable carbohydrates abundant in wheat) rather than gluten itself — double-blind gluten challenges often fail to reproduce symptoms reliably.

Symptoms overlap a lot with coeliac disease (bloating, abdominal pain, fatigue, brain fog, diarrhoea) but are generally gut-motility/discomfort-driven rather than caused by structural intestinal damage.

The practical differences

	Coeliac disease	Gluten sensitivity (NCGS)
Immune system	Adaptive autoimmune response	Possible mild innate immune activation
Antibodies	Anti-tTG, anti-endomysial present	Absent
Intestinal damage	Villous atrophy	None detectable
Genetic marker	HLA-DQ2/DQ8 (almost always present)	No consistent marker
Diagnosis	Blood test + intestinal biopsy	Diagnosis of exclusion (rule out coeliac and wheat allergy first)
Gluten threshold	Trace amounts matter, lifelong strict avoidance needed	Often dose-dependent, some tolerance possible
Long-term risk if untreated	Nutrient deficiencies, osteoporosis, increased lymphoma risk	No known long-term structural damage

One clinically important note: if someone suspects coeliac disease, they need to keep eating gluten until testing is complete — going gluten-free first can normalise the antibodies and biopsy, leading to a false negative.

The genetics in detail

HLA-DQ2 and HLA-DQ8 are variants of genes in the HLA (human leukocyte antigen) region on chromosome 6 — this region codes for proteins that present fragments of proteins to T-cells, essentially deciding what the immune system "sees" as a threat.

• HLA-DQ2 is present in about 90–95% of people with coeliac disease. It comes in two forms — DQ2.5 (higher risk) and DQ2.2 (lower risk) — depending on which gene combination someone inherits.

• HLA-DQ8 accounts for most of the remainder.

• A small fraction of coeliac patients (under 5%) carry neither classic variant, suggesting other, less common HLA combinations or genes can also confer risk.

Why the genetics matter but aren't the whole story:

• Roughly 30–40% of the general population carries HLA-DQ2 or DQ8, but only about 1–3% of those carriers ever develop coeliac disease. So the gene is necessary but nowhere near sufficient.

• This is why coeliac disease is described as needing a "second hit" — additional genetic risk factors (non-HLA genes affecting immune regulation and gut barrier function have been identified in genome-wide association studies, though each contributes only a small effect) plus environmental triggers.

• Proposed environmental triggers include: timing and amount of gluten introduction in infancy, gut microbiome composition, gastrointestinal infections (rotavirus infection in infancy has been linked to increased risk), and other physiological stressors like surgery, pregnancy, or severe illness that can act as a trigger for onset in genetically susceptible adults.

• First-degree relatives of someone with coeliac disease have roughly a 10% risk of developing it themselves, reflecting this shared genetic loading.

Genetic testing for DQ2/DQ8 is mainly useful for ruling out coeliac disease — a negative result makes coeliac disease highly unlikely — rather than confirming it, since so many gene-carriers never develop the disease.

The diagnostic pathway

This matters practically, so here's the sequence clinicians typically follow:

1. Serology (blood tests) — while still eating gluten

• Anti-tissue transglutaminase IgA (tTG-IgA): first-line test, good sensitivity and specificity.

• Total IgA level: checked alongside, because some people are IgA-deficient, which would produce a false negative on the tTG-IgA test. If IgA-deficient, labs switch to IgG-based versions of these tests.

• Anti-endomysial antibodies (EMA-IgA): very specific, often used to confirm a positive tTG result.

• Deamidated gliadin peptide (DGP) antibodies: sometimes used, particularly in young children where tTG can be less reliable.

2. Intestinal biopsy — the traditional gold standard

• Performed via upper endoscopy, taking multiple samples from the duodenum (multiple samples matter because damage can be patchy).

• Pathologists grade damage using the Marsh classification, from Marsh 0 (normal) through Marsh 3 (villous atrophy, subdivided into 3a/3b/3c by severity).

• Some paediatric guidelines now allow diagnosis without biopsy if antibody levels are very high (e.g., tTG-IgA >10x the upper limit of normal) plus a positive EMA and consistent symptoms — this varies by country's guidelines.

3. Genetic testing — used selectively, mainly to rule out disease in ambiguous cases (e.g., someone already gluten-free, or discordant serology/biopsy results).

4. Response to gluten-free diet — symptom and antibody improvement over time supports the diagnosis retrospectively, though this isn't used as the primary diagnostic step.

The gluten challenge problem: as mentioned, all of this relies on active gluten consumption (generally the equivalent of a few grams of gluten daily for at least 2–6 weeks) to produce reliable results. Someone who's already cut out gluten before testing may need to reintroduce it under medical guidance — which is unpleasant if they're symptomatic, but necessary for accurate diagnosis.

For NCGS, diagnosis is purely exclusionary: negative coeliac serology/biopsy, negative wheat allergy testing (skin prick or IgE), and then typically a structured elimination and gluten re-challenge (ideally double-blind, placebo-controlled, since nocebo effects are well-documented in this population) to see if symptoms track gluten exposure specifically.

FODMAP mechanisms

FODMAP stands for Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols — a group of short-chain carbohydrates poorly absorbed in the small intestine. Wheat is a major dietary source, specifically because of fructans (an oligosaccharide).

The mechanism, step by step:

1. Poor absorption: Fructans aren't broken down by human digestive enzymes, so they pass through the small intestine largely intact.

2. Osmotic effect: Because they're small, osmotically active molecules, undigested FODMAPs draw water into the intestinal lumen, which can contribute to bloating, distension, and altered stool consistency.

3. Colonic fermentation: On reaching the colon, gut bacteria rapidly ferment these carbohydrates, producing gas (hydrogen, methane, CO2) as a byproduct. In people with normal gut sensitivity, this happens without much issue. In those with visceral hypersensitivity (a hallmark of irritable bowel syndrome and thought to be relevant in a lot of NCGS-diagnosed people), this gas production and distension triggers pain, bloating, and altered motility.

4. Overlap with wheat: Because fructans and gluten protein are both concentrated in wheat, rye, and barley, someone reacting to fructans will feel better on a "gluten-free" diet — because gluten-free products are typically also lower in fructans — without gluten itself being the actual mechanism.

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The evidence for this: Several well-designed crossover trials (people self-identified as gluten-sensitive were given gluten, fructans, or placebo, blinded, in randomized order) found that a substantial proportion of "gluten-sensitive" participants reacted just as strongly, or more strongly, to the fructan-containing challenge as to the actual gluten challenge — and some reacted to placebo too, suggesting a real nocebo component alongside true fructan sensitivity.

Where this leaves NCGS as a category: Current thinking is that "NCGS" is probably not one single mechanism but an umbrella term covering several overlapping populations — some genuine low-grade gluten-related immune reactivity, some FODMAP/fructan sensitivity, some visceral hypersensitivity or IBS-type mechanisms, and some nocebo-driven symptom reporting. This is part of why research in this area has had inconsistent results — it's likely lumping together mechanistically distinct groups under one diagnostic label.

In conclusion Coeliac disease is a top-down immune attack — antigen crosses the barrier, gets flagged by HLA-DQ2/DQ8, and triggers T-cells, cytokines, and antibody production that damage the villi themselves. The gut lining is the casualty.

• NCGS/FODMAP reactions are a bottom-up mechanical and sensory issue — nothing crosses into tissue, nothing gets flagged by the immune system, and the villi stay intact throughout. The discomfort comes from gas, water, and stretch signals to sensitive nerves, not tissue destruction.

In health & happiness,

KIrsty