A review of the long-term use of proton pump inhibitors and risk of celiac disease in the context of HLA-DQ2 and HLA-DQ8 genetic predisposition

Proton pump inhibitors (PPIs) are among the most prescribed and widely used medications; however, the long-term effects of these medications are only beginning to be investigated. Since the introduction of omeprazole in 1989, PPIs have become the first-choice treatment for esophagitis, peptic ulcer disease, Zoster-Ellison syndrome, dyspepsia, and the prevention of ulcers with non-steroidal anti-inflammatory drugs. Recent studies have specifically examined the rise in celiac disease (CD) in this context. This review explores how PPIs may impact the development of CD and highlights the need for additional research into the environmental and genetic factors that influence the development and progression of the disease. A literature search was performed using the keywords celiac disease, proton pump inhibitors, human leukocyte antigen (HLA)-DQ2, HLA-DQ8. The pathogenesis of CD is multifactorial, and human leukocyte antigens are one factor that may contribute to its development. Additionally, pharmaceuticals, such as PPIs, that cause gut dysbiosis have been linked to the inflammatory response present in CD. Recent studies have suggested that the rise in CD could be attributed to changes in the gut microbiome, highlighting the significant role that gut microbiota is proposed to play in CD pathogenesis. Although PPI therapy is helpful in reducing acid production in gastroesophageal disorders, additional information is needed to determine whether PPIs are still an appropriate treatment option with the possibility of developing CD in the future, particularly in the context of HLA-DQ2 and HLA-DQ8 predispositions. This review emphasizes the importance of personalized medicine for individuals with gastroesophageal disorders that require long-term use of PPIs.