Abstract
The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids. Sphingolipids impact cell–cell contacts and function as second messengers. We collected blood and colon tissue samples from UC patients and healthy controls and investigated the sphingolipids and other lipids by LC-MS/MS or LC-QTOFMS. The expression of enzymes of the sphingolipid pathway were determined by RT-PCR and immunohistochemistry. In inflamed colon tissue, the de novo-synthesis of sphingolipids is reduced, whereas lactosylceramides are increased. Reduction of dihydroceramides was due to posttranslational inhibition rather than altered serine palmitoyl transferase or ceramide synthase expression in inflamed colon tissue. Furthermore, in human plasma from UC-patients, several sphinglipids change significantly in comparison to healthy controls. Beside sphingolipids free fatty acids, lysophosphatidylcholines and triglycerides changed significantly in the blood of colitis patients dependent on the disease severity. Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for UC. Several lipids changed significantly in the blood, which might be used as biomarkers for disease control; however, diet-related variabilities need to be considered.
Highlights
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the rectal and colonic mucosa
Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for ulcerative colitis (UC)
We analyzed whether differences in the sphingolipid status could be observed depending on disease severity and medical treatment in UC patients and whether lipids in the blood might be determined as biomarkers for disease control
Summary
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the rectal and colonic mucosa. Beside S1P, several other sphingolipids have been shown to be deregulated in various diseases, especially under inflammatory conditions [12,16,17,18,19] Ceramides and their complex derivatives are main components of membranes and their deregulation impacts cell signaling and the fate of the cell [20]. Findings in various mice deficient of an enzyme in the sphingolipid pathway, indicate that sphingolipids play an important role in the development of ulcerative colitis [27,28,29,30,31,32,33,34,35]. We analyzed whether differences in the sphingolipid status could be observed depending on disease severity and medical treatment in UC patients and whether lipids in the blood might be determined as biomarkers for disease control
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