Juzentaihoto reduces post-partial hepatectomy hyperammonemia by stabilizing intestinal microbiota

We examined the preventive effect of the Kampo medicine Juzentaihoto (JTX) on post-partial hepatectomy-induced hyperammonemia, a frequent and potentially fatal consequence of this surgery for resection of hepatocellular carcinomas. In most cases, these liver tumors are associated with pre-existing liver damage such as cirrhosis or chronic hepatitis. Post-surgical hyperammonemia harms further the remaining liver as well brain and other vital functions. With pre-surgical JTX administration, this post-surgical hyperammonemia is suppressed significantly. To explain this phenomenon, we first hypothesized that JTX prevents further damage of the liver, a site of ammonia metabolism. However, post-surgical liver dysfunction is not improved with JTX. Thus we focused on the other source of ammonia, the intestinal microbiota, as the source of the hyperammonemia. To examine the possible effect of JTX on intestinal microbiota, terminal restriction fragment polymorphism (T-RFLP), a culture-independent microbial analysis, was used to document change in the intestinal microbiota with JTX. We documented that partial hepatectomy changed the intestinal microbiota. Then we demonstrated that with oral JTX administration, this post-surgical change of the intestinal microbiota was not observed even after partial hepatectomy. We also showed that the representative ammonia-producing bacteria, Bacteroides, increased with partial hepatectomy and decreased with JTX administration. Cluster analysis of fecal microbiota suggests that JTX administration stabilized the intestinal microbiota and maintained the pre-surgical microbial analysis environment of the gut. This study suggests that JTX is useful to prevent the clinically significant increases in the serum ammonia levels after partial hepatectomy.