One approach is to focus on the pre-disease state before the development of acute colitis and colitis-associated cancer (CAC). In this study, we investigated time-course gene expression profiles of a mouse model of DSS-induced acute colitis using whole-genome microarrays. We found that 238 genes exhibited elevated fluctuations in a coordinated manner, which was a pre-disease state-specific phenomenon predicted by the dynamical network biomarker (DNB) theory and occurred two days earlier than the onset of the acute colitis. Furthermore, Daikenchuto suppressed the acute colitis and CAC in the mouse models. These 238 genes are related to NK cells which have never been investigated on acute colitis. In addition, the depletion of NK cells with anti-asialo GM1 antibodies ameliorated the acute colitis. Taken together, Daikenchuto treatment has a potential of novel therapeutic strategies targeting the pre-disease state before the development of acute colitis and CAC.