Infection with invasive Shigella species results in intestinal inflammation in humans but no symptoms in adult mice. To investigate why adult mice are resistant to invasive shigellae, 6~8-week-old mice were infected orally with S. flexneri 5a. Shigellae successfully colonized the small and large intestines. Mild cell death was seen but no inflammation. The infected bacteria were cleared 24 hours later. Microarray analysis of infected intestinal tissue showed that several genes that are involved with the sphingosine-1-phosphate (S1P) signaling pathway, a lipid mediator which mediates immune responses, were altered significantly. Shigella infection of a human intestinal cell line modulated host S1P-related genes to reduce S1P levels. In addition, co-administration of S1P with shigellae could induce inflammatory responses in the gut. Here we propose that Shigella species have evasion mechanisms that dampen host inflammatory responses by lowering host S1P levels in the gut of adult mice.