Therapeutic options for coeliac disease: What else beyond gluten-free diet?

Coeliac disease is a chronic and systemic autoimmune condition triggered by gluten ingestion in genetically predisposed subjects. Currently, the only effective treatment available is a strict, lifelong gluten-free diet. However, patients perceive gluten withdrawal as an unsustainable burden in their life and some of them can exhibit persistent symptoms despite a strict diet. Thus, gluten-free diet represents a challenge, leading scientists to look for alternative or complementary treatments. This review will focus on non-dietary therapies for coeliac disease highlighting six therapeutic strategies: (1) decreasing gluten immunogenic content before it reaches the intestine; (2) sequestering gluten in the gut lumen before absorption; (3) blocking the passage of gluten through a leaky intestinal barrier; (4) preventing the enhancement of immune response against gliadin; (5) dampening the downstream immune activation; (6) inducing immune tolerance to gluten. Most developing therapies are only in the pre-clinical phase with only a few being tested in phase 2b or 3 trials. Although new approaches raise the hope for coeliacs giving them a chance to come back to gluten, for the time being a cautionary appraisal of new therapies suggests that they may have a complementary role to gluten withdrawal, mainly to prevent inadvertent gluten contamination.