What Actually Causes GERD and Acid Reflux? Why Long-Term PPI Use Often Makes It Worse — What long-term PPI use actually does

PPIs work by irreversibly inhibiting the H+/K+ ATPase pump in gastric parietal cells, the final step in gastric acid secretion. The inhibition is profound. PPI use typically reduces gastric acid output by 80-95%. The resulting hypochlorhydria has significant downstream consequences. Consequence 1: SIBO development Gastric acid is the principal bacterial defense of the upper GI tract. The acidic gastric environment (pH 1.5-3.5 in the unmedicated stomach) kills most bacteria that arrive with food or saliva. When PPI use raises gastric pH above 4-5, this defense is substantially compromised. Bacteria that would have been killed survive and can colonize the small intestine, contributing to SIBO development. Multiple studies have documented elevated SIBO prevalence in patients on long-term PPI therapy. Meta-analyses suggest the prevalence is approximately 2-3 fold higher in PPI users compared to controls. The mechanism is direct and well-established. The clinical irony is that the PPI prescribed to treat reflux symptoms can contribute to the development of SIBO, which then produces more reflux through the mechanism described in Mechanism 1. The patient gets sicker over time while symptomatically managed. This is one of the most important reasons to address GERD mechanistically rather than only suppressively. Consequence 2: Nutrient malabsorption Gastric acid is required for the abso