Production of pipecolic acid from intestinal bacteria: Plasma levels of pipecolic acid in patients with liver cirrhosis decreased after oral kanamycin administration

Abstract

We analyzed the changes in plasma levels of pipecolic acid before and after the oral administration of kanamycin in patients with liver cirrhosis and investigated the relationship between plasma pipecolic acid and clinical laboratory tests. Twenty patients received oral kanamycin 1.5 – 3.0 g/day for 7–14 days. Plasma levels of pipecolic acid, which were determined by high-performance liquid chromatography after dansyl derivatization, significantly decreased following kanamycin administration (before 3.16 ± 2.91 nmol/ml, after 2.37 ± 2.48 nmol/ml; P = 0.0002). In addition, plasma ammonia concentration also decreased, although there were no significant changes in plasma lysine and the BCAA AAA ratio. Plasma pipecolic acid correlated closely with plasma ammonia concentration ( P < 0.0001), but not with other hepatic function tests such as ICGR 15, serum albumin, prothrombin time, the BCAA AAA ratio, lysine and serum bilirubin. Plasma levels of pipecolic acid in patients with esophageal varices were significantly higher than those without esophageal varices ( P = 0.032). Plasma level of pipecolic acid in a patient with cirrhosis complicated with hepatic encephalopathy was lowered after kanamycin administration concomitantly with the remission of hepatic encephalopathy. These results show that plasma pipecolic acid is derived in part from intestinal bacteria and is correlated with the degrees of porto-systemic shunt volume.