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

Yichao Shi; Jianfeng Li; Shuntian Cai; Hong Zhao; Huijun Zhao; Gang Sun; Yunsheng Yang

doi:10.3389/fcimb.2023.1205348

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

Front Cell Infect Microbiol. 2023 Aug 17:13:1205348. doi: 10.3389/fcimb.2023.1205348. eCollection 2023.

Authors

Yichao Shi^{1

2}, Jianfeng Li², Shuntian Cai², Hong Zhao³, Huijun Zhao², Gang Sun², Yunsheng Yang^{2

4}

Affiliations

¹ Department of Gastroenterology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
² Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
³ Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
⁴ National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China.

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 Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida 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 Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella 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 Candida in the gastric mucosa in GERD patients.

Keywords: Candida; fecal mycobiota; gastric mucosal mycobiota; gastroesophageal reflux disease; proton pump inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Candida
Dysbiosis
Feces
Gastroesophageal Reflux* / drug therapy
Humans
Proton Pump Inhibitors* / adverse effects

Substances

Proton Pump Inhibitors

Grants and funding

YY has received support from the Key Project of PLA Healthcare Program China (No. 18BJZ33), which supported the study design, collection, analysis, interpretation of data, and decision to submit it for publication; YS has received support from the Medical and Health Research Project of Aerospace Science and Industry Corporation of China (No. 2020-LCYL-010) and the Science Foundation of Aerospace Center Hospital (No. YN202110), which supported the data analysis, writing of this article, and the decision to submit it for publication.