Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease

Abstract

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified <i>Candida</i> at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, <i>Candida</i>, <i>Nothojafnea</i>, <i>Rhizodermea</i>, <i>Ambispora</i>, and <i>Saccharicola</i> were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of <i>Candida</i> in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in <i>Candida</i> colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of <i>Alternaria</i>, <i>Aspergillus</i>, <i>Mycenella</i>, <i>Exserohilum</i>, and <i>Clitopilus</i> in the s-PPI group. In addition, there was a significantly higher abundance of <i>Alternaria</i>, <i>Aspergillus</i>, <i>Podospora</i>, <i>Phallus</i>, and <i>Monographella</i> in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of <i>Candida</i> in the gastric mucosa in GERD patients.