Although the composition of the gut microbiota has been shown to be influenced by host genetics and environmental factors, the effects of the host on the functions of microbial communities remain poorly understood. Intestinal epithelial cells (IECs) exert front line responses to the gut microbiota for maintaining intestinal homeostasis. This study was to elucidate whether IECs modulate Lactobacillus rhamnosus GG (LGG) functions by examining the production of p40, an LGG-derived secretory protein with protective effects on IECs for ameliorating colitis.