Introduction

The intestinal microbiota consisting of the complex and dynamic communities of microbes is a component of the human ecosystem, which profoundly influences health through effects on nutrition, immunity, intestinal epithelial homeostasis and intestinal development. However, the composition of the ‘normal healthy intestinal microbiota’ is not currently clearly defined. Likewise, the characteristics of the host–microbial interaction that contribute to beneficial effects on human health and disruption of this interaction that leads to various disease states are poorly understood. Recent studies using metagenomic analysis of gut microbiome have identified unique bacterial genome sequences that functionally associate with host health.1 2 Furthermore, analysis of the known bacterial genomic sequences, such as Lactobacillus strains, predicts secreted and cell surface proteins with potential regulatory effects on intestinal cells.3 4 Therefore, functional studies of microbe-derived proteins are needed to determine whether the nature of the microbe-derived molecules is as important as the specific microbial composition of the gut. For example, two novel Lactobacillus rhamnosus GG (LGG)-derived proteins have been cloned and shown to prevent cytokine-induced intestinal injury and apoptosis.5

Regulation of signalling pathways to induce diverse cellular responses serves as one of the mechanisms by which microbes and microbial products exert their action on the host. Intestinal microbial regulation of nuclear factor (NF)-κB signalling is one of the best-studied pathways determining intestinal homeostasis and diseases. NF-κB is a key transcriptional factor controlling the expression of genes mediating inflammatory and anti-apoptotic responses (reviewed by Hayden et al6). Growing evidence suggests that ‘optimal’ NF-κB activity plays a significant role in maintaining normal intestinal homeostasis. However, hyper-activation of NF-κB results in chronic intestinal inflammatory disorders (reviewed by Spehlmann and Eckmann7).

It is well known that toll-like receptors (TLRs), a class of membrane receptors that sense extracellular microbes through recognition of microbial products, trigger …