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

Abstract

BackgroundGastric 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.ResultsOmeprazole 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.ConclusionsDespite 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-605) contains supplementary material, which is available to authorized users.

Akkermansia muciniphila and its role in regulating host functions

“…Another widely used drug, the proton pump inhibitor omeprazole, was shown to decrease the abundance of Akkermansia spp. in mice [69]. However, this has not been noted in a recent human study where the effect of proton pump inhibitors had some impact on bacteria other than Akkermansia [70].…”

Alterations in Intestinal Microbiota Correlate With Susceptibility to Type 1 Diabetes

“…How these changes may be involved in disease progression is unclear. The abundance of the Firmicutes genus Coprococcus was shown to be elevated in Crohn disease and decreased in HIV individuals (54), whereas taxa that belong to Butyricimonas , Butyrivibrio , and Akkermansia were linked with the synthesis of short-chain fatty acids (55–57). …”

Interactions between multiple helminths and the gut microbiota in wild rodents

“…abundances were correlated with a decrease of several Firmicutes ( Lactobacillus ) OTUs, whereas the opposite (but non-significant) change was observed with H. polygyrus infection. The most striking pattern was an increase in the unidentified bacteria, S24–7 OTUs (a member of the phylum of Bacteroidetes with potential effects on host health; [ 53 ]) in mice infected by the cestode Hymenolepis spp. In addition, Hymenolepis spp.…”