Background: Functional dyspepsia is a highly prevalent gastrointestinal disorder characterized by chronic upper abdominal symptoms in the absence of structural abnormalities. Proton pump inhibitors (PPIs) are the primary pharmacological intervention, but emerging evidence suggests they may significantly alter the gut microbiome, potentially exacerbating underlying pathophysiological mechanisms.

Objective: This study aimed to evaluate the impact of an eight-week PPI regimen on gut microbiota diversity and gastrointestinal symptom severity in patients with functional dyspepsia.

Method: A simulated prospective cohort study was conducted using synthesized academic training data from 250 patients diagnosed with functional dyspepsia according to Rome IV criteria. Patients received pantoprazole 40 mg daily for eight weeks. Stool samples were collected at baseline and at eight weeks for 16S rRNA gene sequencing to assess microbial diversity. Gastrointestinal symptoms were quantified using the Gastrointestinal Symptom Rating Scale (GSRS).

Results: PPI therapy resulted in a significant reduction in gastric acid suppression-related symptom scores, with the total GSRS score decreasing from 4.2 to 2.8 (p < 0.001). However, alpha diversity metrics, specifically the Shannon index (mean decrease of 0.45, p = 0.002) and Chao1 index (mean decrease of 18.4, p = 0.005), significantly declined. There was a notable enrichment of oral commensal bacteria, particularly Streptococcaceae, in the gut microbiome post-treatment.