What Causes Celiac Disease?

One of the most common questions I hear from patients is What actually causes celiac disease? And the follow-up is almost always the same: How did I eat gluten my entire life and then suddenly get sick from it?

These are fair questions, and honestly, for a long time, medicine didn’t have answers. That’s changing. Researchers have made meaningful progress, and what they’re finding matters, not just for people already diagnosed, but for anyone with a family history or a nagging suspicion that something isn’t right.

Here’s what we know: celiac disease doesn’t happen by accident. Three specific things must be present at the same time. Take away any one of them, and celiac disease cannot develop.

1. You Have to Be Eating Gluten

This one sounds obvious, but it’s worth clarifying. The immune reaction that happens with celiac disease requires gluten to be present in your diet. No gluten, no active celiac disease, it’s that straightforward. This doesn’t mean that celiac disease goes away if you stop eating gluten, but rather, if you never in your life ate gluten, you would never develop celiac disease.

Gluten is a protein found naturally in wheat, rye, and barley. And in the Western diet, wheat is everywhere: bread, pasta, cereals, crackers, soups, sauces, processed foods, the list goes on. Despite how mainstream gluten-free eating has become, most Americans are still consuming wheat multiple times a day without thinking twice about it.

For someone genetically predisposed to celiac disease, that daily exposure is the starting point for everything that follows.

2. You Must Carry the Gene

However, eating gluten isn’t enough to cause celiac disease on its own. Celiac disease also requires someone to carry at least one of two genes associated with celiac disease. What’s interesting is that these genes are actually fairly common. Somewhere between 30 and 40 percent of the general population carries one of them. But here’s the catch: carrying one of these genes doesn’t mean you’ll develop celiac disease. Only about five percent of people with one or both of the genes ever do. That’s why celiac disease can skip generations in a family, or why one sibling gets diagnosed while another never has a problem. The gene creates possibility; it doesn’t guarantee a celiac diagnosis. However, if you do not carry one of the genes, it is incredibly rare ( less than 1 % chance)  to develop celiac disease.

3. Something Has to Trigger It

This is where it gets complicated, and where researchers are doing some of the most interesting work. Even if someone is eating gluten and carries the gene, celiac disease still needs something to activate it. A trigger.

We don’t fully understand what that trigger is in every case, but several factors have been identified as potential culprits:

• Pregnancy
• A serious illness
• Menopause
• Antibiotic use
• The acne medication isotretinoin (sold as Accutane in the U.S. until 2009)
• Long-term use of NSAIDs like ibuprofen
• Gastrointestinal infections

What’s striking about this list is how ordinary most of these things are. A round of antibiotics. A bad stomach bug. A pregnancy. These are normal life events, which may be exactly why celiac disease can seem to appear out of nowhere in someone who’s eaten gluten without issue for 30 or 40 years.

One of the most compelling areas of current research involves viral infections as a potential trigger. Studies suggest that certain viruses can cause the immune system to overreact, and if that reaction is prolonged or repeated, it may cause a person to lose their tolerance for gluten.

Researchers have also found that different people with celiac disease show different immune responses to the same infection, a discovery that may help explain why celiac symptoms vary so dramatically from one person to the next. Some experience digestive distress, while others develop skin conditions, neurological symptoms, or nutrient deficiencies with little to no gut involvement.

Rotavirus, in particular, has been identified as one virus more likely to trigger these immune responses. This finding has significant implications: a rotavirus vaccine already exists. If rotavirus is confirmed as a trigger, that widely available vaccination could potentially help prevent celiac disease in genetically susceptible individuals, particularly children and relatives of people already diagnosed, who face a higher-than-average risk.

First-degree relatives of someone with celiac disease, parents, siblings, and children, have a significantly higher risk of developing the condition themselves. Understanding this helps explain why screening is so important for this group, even in the absence of obvious symptoms.

Celiac disease is notoriously underdiagnosed. Many people live with it for years, experiencing symptoms that get attributed to other conditions. Knowing that a specific combination of factors causes celiac disease rather than it being a random occurrence gives both patients and physicians a clearer roadmap for identifying who is most at risk.

The celiac research community is increasingly focused on prevention, not just treatment. While a strict gluten-free diet remains the only effective management strategy today, identifying the environmental triggers of celiac disease opens the door to something more powerful: stopping it before it starts.

Vaccination against viral triggers, microbiome-based interventions, and early genetic screening are all being explored. These possibilities may sound distant, but science is moving faster than many people realize. For the millions of people with a family history of celiac disease and the many more who carry the genetic markers without knowing it, that progress represents real hope.