The Japanese traditional medicine TU-100 and one of its constituent components, ginger, inhibited enteropooling in both the SPF and GF mice. Therefore our studies demonstrate that gingerols or shogaols are the active agents in TU-100 that inhibit inflammation in this model. Additionally, as the effects were observed in germ free mice, the actions of these agents are also independent of intestinal bacteria. Several signal transduction proteins activated in this model are blocked by TU-100 or ginger, including Akt and NF-kB. We demonstrate that anti-CD3 antibody activation of Akt and subsequent stimulated production of TNFa by CD4 + lamina propria lymphocytes are relevant in this model. Additionally, the enteropooling effect requires epithelial cell NF-kB activation, therefore both the CD3 + CD4 + T cells and intestinal epithelial cells are likely to affected by TU-100. The studies demonstrate for the first time that anti-CD3 antibody induction of enteritis is independent of microbes. We also demonstrated that TU-100 or its constituent compound ginger exert therapeutic efficacy to block this enteritis. Among the diakenchuto components, the gingerols/shoagaols and sanshools are not known to require microbial metabolism for activity. Our study would also support this conclusion. Gingerols/shoagaols and sanshools are rapidly absorbed within 30 minutes after TU-100 ingestion, suggesting this occurs in the proximal gastrointestinal tract prior to exposure to the majority of the intestinal microbiome that resides in the colon. In contrast for ginseng, it is known that many ginseng compounds require bacterial metabolism, such as conversion of ginsenoside Rb1 to compound K, as well as other ginsenoside conversions. We and others have shown that compound K has potent anticancer effects mediated by the microbial metabolites of certain ginsenosides. This is only the second study to investigate the actions of TU-100 on small intestinal inflammation. A prior study had shown that small intestinal damage induced by the drug CPT- 11 is also inhibited by TU-100. Whether TU-100 can be used to treat other small bowel inflammatory diseases such as viral enteritis or Celiac disease remains to be determined. Further studies are needed to determine the mechanism by which gingerols or shogaols inhibit Akt and NF-kB. It is possible that the effects of ginger as well as TU-100, may be due to their antioxidant activities which could also inhibit NF-kB and Akt signals.