I read an excellent and interesting study by Dr. Ewaschuk and colleagues1 showing the beneficial effects of probiotic compounds on colonic barrier function and the protection of liver in a mouse model of sepsis. The author revealed that a pretreatment with oral probiotics for 7 days could prevent the breakdown in intestinal barrier function, bacterial translocation, and hepatic damage in interleukin-10 (IL-10) gene-deficient mice with sepsis induced by coinjection of 360 mg/kg D-galactosamine (GalN) and 40 μg/kg lipopolysaccharide (LPS). GalN is a hepatotoxic agent, which leads to rapid depletion of uridine nucleotides, resulting in an impaired biosynthesis of macromolecular cell constituents such as RNA, membrane glycoproteins, and glycogen in hepatocytes. It has been reported that coinjection of GalN and a low dose of LPS (1-10 μg/kg) lead mice to irreversible septic shock, fulminant hepatitis with severe hepatic congestion, and rapid death within 5-9 hours after injection.2, 3 In the article, the authors mention that the mice were killed 6 hours after injection for analysis according to the results of preliminary dose-dependent studies. A septic mouse used for this experiment has characteristics of a patient dying from severe septic shock and hepatic failure, which seems not to be suitable for a study to evaluate the usefulness of probiotics. I would like to ask the authors to show the survival data of mice and whether the effects of oral probiotics on survival were investigated.
In the Editorial on this paper,4 Dr. Versalovic speculates that the egress of proinflammatory mediators from leaky gut into the portal circulation contributed to hepatic injury. We previously compared the levels of IL-1, IL-6, and LPS in the systemic circulation with those in the portal blood during major abdominal surgery.5, 6 No difference was found among them, and modest endotoxemia induced by surgical stress was not correlated with hepatic injury. Although the advantages of probiotic administration in the protection of intestinal epithelium have been confirmed, the relationship between moderately increased intestinal permeability and liver damage has not been elucidated.