Biomaterial Database

Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria. 2018

Eiichiro Yasutomi, and Namiko Hoshi, and Soichiro Adachi, and Takafumi Otsuka, and Lingling Kong, and Yuna Ku, and Haruka Yamairi, and Jun Inoue, and Tsukasa Ishida, and Daisuke Watanabe, and Makoto Ooi, and Masaru Yoshida, and Tomoya Tsukimi, and Shinji Fukuda, and Takeshi Azuma

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chu-o-ku, Kobe, Hyogo, 650-0017, Japan.

Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it. Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration. Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution. Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D003092	Colitis	Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.	Colitides
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004756	Enterobacteriaceae Infections	Infections with bacteria of the family ENTEROBACTERIACEAE.	Enterobacterial Infections,Cronobacter Infections,Infections, Enterobacteriaceae,Infections, Enterobacterial,Cronobacter Infection,Enterobacteriaceae Infection,Enterobacterial Infection,Infection, Cronobacter,Infection, Enterobacteriaceae,Infection, Enterobacterial,Infections, Cronobacter
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D044082	Citrobacter rodentium	A species of gram-negative bacteria in the genus CITROBACTER, family ENTEROBACTERIACEAE. As an important pathogen of laboratory mice, it serves as a model for investigating epithelial hyperproliferation and tumor promotion. It was previously considered a strain of CITROBACTER FREUNDII.	Citrobacter freundii Biotype 4280
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D054328	Proton Pump Inhibitors	Compounds that inhibit H(+)-K(+)-EXCHANGING ATPASE. They are used as ANTI-ULCER AGENTS and sometimes in place of HISTAMINE H2 ANTAGONISTS for GASTROESOPHAGEAL REFLUX.	Proton Pump Inhibitor,Inhibitor, Proton Pump,Inhibitors, Proton Pump,Pump Inhibitor, Proton
D064747	Lansoprazole	A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.	Lansoprazoles,2-(((3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl)methyl)sulfinyl)benzimidazole,AG 1749,AG-1749,Agopton,Bamalite,Lansol,Lansoprazol,Lansoprazole Sodium,Lanzor,Monolitum,Ogast,Ogastro,Opiren,Prevacid,Prezal,Pro Ulco,Promeco,Takepron,Ulpax,Zoton,AG1749,Sodium, Lansoprazole