The effect of omeprazole on the development of experimental autoimmune encephalomyelitis in C57BL/6J and SJL/J mice

BMC Research Notes

Steven M LeVine²  Aaron C Ericsson³  Brooks L Parker¹  Thomas M Yankee¹  Sheila Tsau²  Scott A Sands² 

[1] Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd, 66160 Kansas City, KS, USA;Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City 66160, KS, USA;Department of Veterinary Pathobiology, Mutant Mouse Regional Resource Center, University of Missouri, 4011 Discovery Drive, 65201 Columbia, MO, USA

关键词: T cells;    Proton pump inhibitor;    Multiple sclerosis;    Coprococcus;    Bacteroidales;    Akkermansia muciniphila;   

Others  :  1129825
DOI  :  10.1186/1756-0500-7-605

 received in 2014-08-25, accepted in 2014-08-29,  发布年份 2014

【 摘 要 】

Background

Gastric disturbances such as dyspepsia are routinely encountered by multiple sclerosis (MS) patients, and these conditions are often treated with gastric acid suppressors such as proton pump inhibitors, histamine H2 receptor antagonists, or antacids. The proton pump inhibitor omeprazole can alter the gut flora and immune responses, both of which can influence the course of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The objective of the current study was to examine the effect of omeprazole treatment on the development of EAE. Bacterial microbiome analysis of mouse fecal pellets was determined in C57BL/6J EAE mice chronically treated with omeprazole, and spleen immune cell content, clinical scores, weight, rotarod latency, and histopathology were used as outcome measures in C57BL/6J and SJL/J mice with EAE.

Results

Omeprazole treatment resulted in decreases in Akkermansia muciniphila and Coprococcus sp. and an increase in unidentified bacteria in the family S24-7 (order Bacteroidales) in C57BL/6J mice with EAE. Omeprazole did not alter spleen immune cell content compared to vehicle in EAE mice, but differences independent of treatment were observed in subsets of T cells between early and advanced disease in C57BL/6J mice as well as between the two strains of mice at an advanced disease stage. Omeprazole caused no difference in clinical scores in either strain, but significantly lowered weight gain compared to vehicle in the C57BL/6J mice with EAE. Omeprazole also did not alter rotarod behavior or hindbrain inflammatory cell infiltration compared to vehicle in both strains of mice with EAE. Rotarod latency did reveal a negative correlation with clinical scores during active disease in both mouse strains, but not during clinical remission in SJL/J mice, suggesting that rotarod can detect disability not reflected in the clinical scores.

Conclusions

Despite alterations in the gut microbiota and weight gain in the C57BL/6J EAE model, omeprazole had no effect on multiple measures of disease activity in C57BL/6J and SJL/J mice with EAE, supporting the notion that omeprazole does not substantially influence disease activity in MS patients.

【 授权许可】

   
2014 Sands et al.; licensee BioMed Central Ltd.

【 图 表 】

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