Why Is Gluten Intolerance on the Rise?

Celiac disease incidence has been climbing steadily across the Western world since at least the mid-twentieth century, and the trend is too steep to be explained by better diagnostic tests alone. A systematic review and meta-analysis published in the American Journal of Gastroenterology confirmed that the rise is real and significant, spanning multiple decades and countries.¹ But the story behind the numbers involves far more than gluten itself. Changes in how food is processed, what happens in the gut during infancy, shifts in the microbiome, viral infections, and even chemicals sprayed on crops all appear to play a role.

The Increase Is Not Just Better Diagnosis

One of the first things skeptics point out is that doctors are simply getting better at catching celiac disease and non-celiac gluten sensitivity. That is partly true. Blood tests for tissue transglutaminase antibodies became widely available in the 1990s, and awareness among physicians has grown considerably since then. But studies that retest archived blood samples from decades past, using the same modern assays, still find that celiac disease was genuinely less common in previous generations. The meta-analysis covering the latter half of the twentieth century and into the twenty-first century found a significant upward trend in incidence across the Western world, even after accounting for improved detection.¹ Something environmental is changing, because human genetics do not shift that fast.

Modern Wheat Breeding Is Not the Culprit

A popular explanation pins the blame on modern wheat varieties, claiming that decades of selective breeding have loaded grain with extra gluten. The evidence says otherwise. Research comparing heritage and modern bread wheat has consistently found that protein content in modern varieties has actually gone down over time, while starch content has increased.² Ancient wheats tend to contain more protein, more gluten, and greater quantities of the specific gluten fragments that trigger celiac immune responses.²

A separate analysis grouping wheat cultivars by their release period found that older varieties had significantly higher levels of immunogenic gluten epitopes than modern ones.³ Another study looking specifically at U.S. wheat concluded that breeding has not increased the gluten content of American wheat over the decades.⁴ So if you are reaching for an artisan “ancient grain” loaf hoping it is gentler on your gut, you may be getting more of the very proteins that cause trouble. The variability within any era’s wheat is enormous, though, which is why blanket claims about old versus new grain are unreliable. The specific variety matters more than when it was released.

How Industrial Food Processing Changes the Picture

Where modern food does differ dramatically from what your great-grandparents ate is in how it is processed. Two shifts stand out.

The first involves fermentation. Traditional bread-making relied on long sourdough fermentation, which partially breaks down gluten proteins. Certain lactic acid bacteria can degrade the proline-rich peptides in gluten that are hardest for human digestive enzymes to handle. Research has found that mixed cultures of these bacteria are more effective than single strains at chewing through immunogenic gluten fragments.⁵ However, sourdough alone does not reduce gluten below the safety threshold for people with celiac disease. That goal is only achieved when sourdough fermentation is combined with fungal enzymes during the process.⁵ Modern commercial bread, by contrast, often uses fast-rise yeast and minimal fermentation time, skipping the partial gluten breakdown that traditional methods provided. Even when sourdough cultures are used, the fermentation changes how gluten proteins behave during digestion rather than eliminating them outright.⁶

The second shift involves a food additive called microbial transglutaminase, an enzyme widely used in processed foods to improve texture, bind proteins together, and extend shelf life. Think of it as a “protein glue.” It cross-links gliadin peptides from gluten into new complexes that do not occur in nature.⁷ Because microbial transglutaminase belongs to the same enzyme family as tissue transglutaminase, the enzyme targeted by the immune system in celiac disease, it can mimic tissue transglutaminase and is recognized by celiac antibodies.⁸ A review of the evidence describes microbial transglutaminase and its modified complexes as pro-inflammatory, immunogenic, and potentially pathogenic, raising public health concerns that contrast sharply with manufacturers’ safety claims.⁹ This additive is in bakery products, processed meats, dairy, and imitation seafood, which means many people with a genetic susceptibility to celiac disease are encountering these novel gluten-enzyme complexes daily.

What Happens in the Gut During Infancy

Several early-life exposures appear to set the stage for whether someone develops gluten intolerance later. Timing of first gluten exposure is one piece. A meta-analysis found that introducing gluten after six months of age was linked to a roughly 25% increased risk of celiac disease compared to introducing it between four and six months.¹⁰ Introducing it too early also appears risky. A study of genetically at-risk children found that exposure to gluten-containing foods in the first three months of life carried a dramatically higher risk of celiac autoimmunity compared to the four-to-six-month window.¹¹ There seems to be a window during which the infant immune system is primed to learn tolerance to dietary proteins. Miss that window in either direction, and the odds shift.

Antibiotics during infancy are another factor. A large pooled analysis from Scandinavian cohorts found that children who received systemic antibiotics in their first year of life had about a 26% higher odds of developing celiac disease, with a dose-response relationship: each additional course of antibiotics nudged the risk up further.¹² A more recent population-based study confirmed this pattern, finding that ten or more antibiotic prescriptions in the first year were associated with over 40% higher risk of celiac autoimmunity.¹³ Acid-suppressing medications in infancy, such as proton pump inhibitors and H2 blockers, also appear to raise the hazard.¹⁴ The likely mechanism is disruption of the developing gut microbiome at a critical period, altering which bacteria colonize the intestine and how the immune system learns to handle food proteins.

Viral Infections as a Trigger

An unexpected contributor is a common, usually harmless virus. Reovirus, which most people encounter in childhood without noticeable illness, can disrupt the way the immune system develops tolerance to food proteins. In mouse studies, reovirus infection suppressed the regulatory immune cells that normally teach the body to accept dietary proteins as safe, while ramping up inflammatory responses to those same proteins.¹⁵ Not all reovirus strains do this equally. One strain broke oral tolerance while another did not, and the difference depended on how strongly the virus activated natural killer cells and interferon signaling in the gut’s lymph nodes.¹⁶

This means that the timing of a viral infection relative to when a child first encounters gluten could matter as much as the gluten exposure itself. If the immune system is in an inflammatory state from a gut virus when it first meets gliadin proteins, it may learn to treat gluten as a threat rather than food. This is difficult to track in humans, but it offers a plausible reason why genetically identical twins sometimes diverge, with one developing celiac disease and the other not.

The Microbiome and Gluten Digestion

Gluten is unusually hard for humans to digest. Its high proline content makes it resistant to the enzymes in your stomach and small intestine, leaving large, intact peptide fragments that can provoke an immune reaction. Your gut bacteria, however, produce their own set of enzymes that can pick up where human digestion leaves off. Certain species, including members of the Lactobacillus, Bifidobacterium, and Prevotella families, produce enzymes capable of breaking down those stubborn proline-rich fragments.¹⁷

A systematic review found that people with celiac disease and non-celiac gluten sensitivity show altered levels of these gluten-digesting microbial enzymes compared to healthy controls.¹⁸ The implication is that if your microbiome lacks the right bacterial communities, more undigested gluten fragments survive to reach the intestinal wall, where they can trigger inflammation. Reduced microbial diversity, driven by factors like antibiotic use, ultra-processed diets, and less exposure to environmental microbes, may be stripping away a layer of protection that populations with traditional diets still benefit from.¹⁷

When those partially digested gluten fragments reach the intestinal lining, they bind to a receptor called CXCR3, triggering the release of a protein called zonulin that loosens the tight junctions between intestinal cells.¹⁹ This increased intestinal permeability, sometimes called “leaky gut,” allows gluten fragments and bacterial products to slip through into the body, where they can activate the immune system more aggressively. In people with celiac disease, this process spirals into full-blown autoimmune destruction of the intestinal lining.

It May Not Even Be Gluten

Here is where the picture gets genuinely confusing, even for researchers. Many people who believe they are gluten-sensitive are reacting to something else in wheat. A well-designed crossover trial gave people with self-reported non-celiac gluten sensitivity either purified gluten, fructans (a type of fermentable carbohydrate found in wheat), or a placebo. Fructans produced significantly worse symptoms than gluten, and there was no meaningful difference between gluten and placebo.²⁰

Non-celiac gluten sensitivity, as researchers increasingly recognize, is probably an umbrella term covering reactions to several different wheat components. Besides fructans, wheat contains amylase-trypsin inhibitors, or ATIs, which are pest-resistance molecules that activate innate immune responses through a completely different pathway than the one involved in celiac disease.²¹ ATIs fire up inflammatory signaling in immune cells from both celiac and non-celiac individuals, and they do so through TLR4, a receptor involved in the body’s response to bacterial infection.²² Wheat germ agglutinin and even glyphosate residues have also been proposed as contributing factors.²³ Research characterizing non-celiac wheat sensitivity has found evidence of systemic immune activation and intestinal barrier defects, suggesting a genuine biological condition even though gluten may not be the primary trigger.²⁴

This distinction matters practically. If your real trigger is fructans, going gluten-free will help only because gluten-free products also happen to be fructan-free. But you might do just as well on a low-FODMAP diet that still includes some gluten-containing foods, and you would avoid the nutritional trade-offs and expense of strict gluten avoidance.

Glyphosate and Gut Health

The herbicide glyphosate, used heavily on conventional wheat (often sprayed shortly before harvest to dry the crop), has drawn attention as a possible environmental factor. A systematic review found that glyphosate and its commercial formulations can disrupt intestinal microbial balance, alter gut permeability, and damage the mucus layer and microvilli that line the intestine.²⁵ Animal studies have shown that glyphosate exposure increases gut inflammation and permeability, with effects more pronounced in the large intestine.²⁶ In piglet studies, glyphosate reduced expression of tight junction proteins in the small intestine, contributing to oxidative stress.²⁷

The evidence here is mostly from animal models, and researchers are cautious about extrapolating directly to humans eating typical dietary levels. But the mechanism is biologically plausible: if glyphosate residues weaken the intestinal barrier and alter the microbiome, they could lower the threshold at which gluten or other wheat components cause problems. The rise in glyphosate use over the past few decades roughly parallels the increase in celiac diagnosis, though correlation alone does not prove causation.

The Nocebo Problem and Unreliable Testing

Not every person who avoids gluten is genuinely intolerant. When researchers ran double-blind, placebo-controlled gluten challenges on people who had self-diagnosed with non-celiac gluten sensitivity, only about 16% showed symptoms specific to gluten. Meanwhile, 40% of participants reacted just as strongly, or more strongly, to the placebo.²⁸ This nocebo effect, where expecting symptoms produces them, is a powerful force in food-sensitivity research and contributes to the perception that gluten intolerance is more widespread than the biology supports.

The commercial food-sensitivity testing market has not helped. Direct-to-consumer tests that claim to identify food intolerances based on IgG antibodies are largely misleading. A review found that most of these products come from unaccredited laboratories using methodology that mainstream allergy specialists consider unreliable.²⁹ IgG antibodies to food proteins are a normal part of immune function and do not indicate intolerance. But when a test report comes back flagging wheat, dairy, and eggs, many people eliminate those foods and attribute any subsequent improvement to the test’s accuracy, even when the improvement may be due to eating more carefully in general or simply to the passage of time.

Genetics Set the Stage but Cannot Explain the Rise

Celiac disease requires specific genetic markers, particularly the HLA-DQ2 and HLA-DQ8 gene variants. A meta-analysis found that celiac patients have significantly higher odds of carrying HLA-DQ2.³⁰ In one study, about 98% of confirmed celiac patients carried one or both of these markers.³¹ But here is the catch: roughly 30 to 40% of the general Western population carries these same gene variants, and only a fraction of them develop celiac disease. Genetics load the gun; something in the environment pulls the trigger. That gap between genetic potential and actual disease is exactly where all the factors discussed above converge. The gene pool has not changed in two generations. The food supply, the microbial environment, infant medical care, and the chemical landscape all have.

What Traditional Food Cultures May Get Right

Some researchers have begun looking at populations with long histories of wheat consumption that maintain relatively low rates of gluten-related disease. A model integrating evidence from microbiology and dietary anthropology suggests that early gluten exposure, high microbial diversity, and cultural food-preparation traditions, including fermentation, all contribute to building and maintaining mucosal tolerance to gluten.¹⁷ In these communities, children encounter gluten through traditionally prepared foods while their microbiomes are still diverse and their immune systems are developing. The contrast with a modern Western infant, who may receive antibiotics, acid suppressants, and highly processed wheat products during the same developmental window, is striking.

This does not mean traditional diets are a cure or that people with celiac disease can eat their way to tolerance. Once the autoimmune process is established, strict gluten avoidance remains the only proven treatment. But the research suggests that the conditions under which populations first encounter and continue to consume wheat, including how it is prepared and what else is living in the gut, shape whether the immune system treats gluten as food or foe. The rise in gluten intolerance likely reflects a convergence of modern disruptions to that ancient arrangement.