Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota.

Gut biological information, including microbiota and metabolites, shows increasing associations with diseases such as inflammatory bowel disease, obesity, and diabetes. Precise sampling and modulation of biological information have become critical in medical research, health assessments, and interventions. Although various intestinal sampling and drug delivery capsules have been developed independently, achieving multifunctional passive capsules within a swallowing size remains a challenge. Here, we have designed a dual‐functional passive capsule that integrates intestinal sampling and drug delivery capabilities through a dual‐control mechanism based on pH responsiveness and mechanical actuation and meets the standard requirements for oral ingestion (Ø10.5 mm × L26 mm). It is engineered to target specific regions of the gut, activating the sampling function in response to pH values (≥5.5). The system enables high‐throughput collection of intestinal juice (>300 μL) while effectively resisting gas interference. An integrated, spring‐driven actuation mechanism provides a sealing force exceeding 0.78 N, ensuring secure encapsulation of collected samples even under the mechanical stresses posed by high‐viscosity intestinal contents (1 × 10 ⁶ mPa s). The capsule's dual functionality was successfully validated in‐vivo using Bama miniature pigs, demonstrating efficient, contamination‐sealed sample collection suitable for downstream sequencing analysis and highlighting its strong potential for biomedical applications.