Relationship Between the Gastrointestinal Side Effects of an Anti-Hypertensive Medication and Changes in the Serum Lipid Metabolome

Abstract

An earlier study using a rat model system indicated that the active ingredients contained in the anti-hypertensive medication amlodipine (AMD) appeared to induce various bowel problems, including constipation and inflammation. A probiotic blend was found to alleviate intestinal complications caused by the medicine. To gain more extensive insight into the beneficial effects of the probiotic blend, we investigated the changes in metabolite levels using a non-targeted metabolic approach with ultra-performance liquid chromatography-quadrupole/time-of-fligh (UPLC-q/TOF) mass spectrometry. Analysis of lipid metabolites revealed that rats that received AMD had a different metabolome profile compared with control rats and rats that received AMD plus the probiotic blend. In the AMD-administered group, serum levels of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, triglycerides with large numbers of double bonds, cholesterols, sterol derivatives, and cholesterol esters (all p < 0.05) were increased compared with those of the control group and the group that received AMD plus the probiotic blend. The AMD-administered group also exhibited significantly decreased levels of triglycerides with small numbers of double bonds (all p < 0.05). These results support our hypothesis that AMD-induced compositional changes in the gut microbiota are a causal factor in inflammation.