The Impact of Long-Term Proton Pump Inhibitor (PPI) Use on Gut Microbiota Composition and Diversity in Patients with Peptic Ulcer Disease: A Literature Review

Abstract

Proton pump inhibitors (PPIs) are a key component of treatment for peptic ulcer disease (PUD) and ulcer healing, as demonstrated by their highly effective acid-suppressing effects. However, their continued use has shown that they can indirectly affect the gut microbiota, a system vital to both digestive and overall health. Evidence suggests that proton pump inhibitors (PPIs) can alter microbial composition and function. The extent of the clinical impact of these changes remains uncertain, especially when patients with PUD often require extended therapy. In this context, the paper examines existing evidence on PPI use and its relationship with the gut microbiome, with particular attention to whether certain microbes emerge more prominently under prolonged use. Across studies, several trends emerge. Microbial diversity declines, oral-origin taxa become increasingly prevalent in the intestine, and protective commensals decline. Such alterations could contribute to dysbiosis-related complications. These findings highlight an important clinical dilemma. While PPIs are highly effective in the treatment and management of PUD, their associated effects on the microbiome are raising concerns about long-term safety. Thus, larger, more targeted studies in PUD groups are needed to address existing knowledge gaps. In addition, strategies for microbial balance protection, therapeutic benefits, and acid suppression are required to preserve microbial homeostasis while maintaining the therapeutic benefits of acid suppression.