Fukui Hirokazu, a professor at Shimadzu Corporation and Hyogo Medical University's Department of Gastroenterology, has developed a method to evaluate intestinal mucosal permeability, an indicator of the pathophysiology of ulcerative colitis and irritable bowel syndrome, using liquid chromatography-mass spectrometry (LC-MS) and the blood concentration of the dye indigo carmine. The method developed this time not only reduces the burden on patients but also enables quantitative evaluation of the pathophysiology, contributing to the elucidation of causes and the development of treatment methods. This research achievement was developed in the "Omics Analysis Course" established by our company at Hyogo Medical University in 2019 and will be presented at the 49th Medical Mass Spectrometry Society (held on September 13-14 at Shimadzu Corporation Headquarters).

The number of ulcerative colitis patients in Japan is approximately 0.2 million, and the number of potential patients with irritable bowel syndrome is approximately 12 million, which is about 10% of the population. When the symptoms worsen, abdominal pain and frequent bowel movements interfere with daily life. The cause is not clear, but it is believed that "leaky gut" caused by increased intestinal mucosal permeability due to impaired intestinal barrier function is one of the factors. It is thought that the penetration of food antigens, intestinal bacteria, and their products into the body through leaky gut leads to the onset of the disease. However, there has been no quantitative evaluation method for mucosal permeability in living human bodies, and research on the mechanism and pathophysiology has not progressed. The lactulose-mannitol method, which evaluates mucosal permeability by measuring the concentration excreted in urine after oral administration of sugars, has been the only method used for evaluating mucosal permeability, but this method requires a day's worth of urine collection, which is a burden on the subjects and has issues such as being affected by gastrointestinal motility, diet, and renal function.

The research group focused on the phenomenon that indigo carmine used in endoscopic examinations is excreted in urine after the examination, and investigated a mucosal permeability evaluation method using this dye. After the examination, the blood concentration of indigo carmine was evaluated for its relationship with the pathophysiology in 11 patients with ulcerative colitis and 5 healthy subjects. Significant differences in concentration were observed in both groups, suggesting the effectiveness of this method. Shimadzu Corporation's liquid chromatography-mass spectrometer "LCMS-8060" was used to measure the blood concentration of indigo carmine. In conventional treatments for ulcerative colitis and irritable bowel syndrome, the therapeutic effect has been measured based on the patients' subjective symptoms after medication. When this new method is put into practical use, it will lead to efficient treatment with reduced burden on patients. Shimadzu Corporation and Hyogo Medical University will continue clinical research on this method to establish its clinical significance. In the future, Shimadzu Corporation aims to cooperate with Hyogo Medical University to obtain clinical evidence for this method and develop research equipment to support drug discovery research and medical devices that can be used in clinical tests.

Photo: Liquid Chromatography-Mass Spectrometer 'LCMS-8060'

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