The presence of commensal flora reduced colonization of Escherichia coli O157:H7 and production of Shiga toxin (Stx) in the murine intestine. Six production was not detected in mice colonized with E. coli that were resistant to the Shiga toxin phage, but it was detected in mice colonized with phage-susceptible E. coli. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article explores the fascinating relationship between the mammalian immune system and the bacteria that are present in the mammalian gut. Every human is an ecosystem that hosts 1013–1014 bacteria. We review the evidence that immunomodulatory molecules produced by commensal bacteria in the gut have a beneficial influence on the development of certain immune responses, through eliciting the clonal expansion of CD4+ T-cell populations. This process seems to contribute to the overall health of the host by offering protection against various diseases and might provide supporting evidence at a molecular level for the 'hygiene hypothesis' of allergic immune disorders.

Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and its commensal microflora. Heterogeneity of disease susceptibility in humans and rodents suggest that multiple mechanisms are responsible for the etiology of IBD. In particular, deficiencies in anti-inflammatory and immune-suppressive mechanisms play an important role in the development of IBD. However, it is unknown how the indigenous microflora stimulates the immune system and how this response is regulated. To address these questions, we investigated the role of Toll-like receptor (TLR) signaling in the development of spontaneous, commensal-dependent colitis in interleukin (IL)-2- and IL-10-deficient mice. We report that colitis was dependent on TLR signaling in Il10(-/-) mice. In contrast, Il2(-/-) mice developed intestinal inflammation in the absence of TLR signaling pathways. These results demonstrate a differential role of innate immune recognition by TLRs in the development of commensal-dependent colitis.

What might bacteria derive from producing this type of lipid A, and what do animals gain from recognizing it? A survey of diverse lipid A structures found that the best-recognized configuration is produced by most of the aerobic or facultatively anaerobic Gram-negative bacteria that can live in the gastrointestinal and upper respiratory tracts. We hypothesize that the CD14–MD-2–TLR4 mechanism evolved to recognize not just pathogens, but also many of the commensals (normal flora) and colonizers that can inhabit the body's most vulnerable surfaces. Producing this lipid A structure seems to favor bacterial persistence on host mucosae, whereas recognizing it allows the host to kill invading bacteria within subepithelial tissues and prevent dissemination. A conserved host lipase can then limit the inflammatory response by removing a key feature of the lipid A signal, the secondary acyl chains.

Humans are not inherently endowed with a healthy immune system. The fate of the immune system depends on its interaction with a large variety of commensal microorganisms, most of which live in the lower gastrointestinal tract.1 How the body maintains homeostasis with an incredibly complex enteric microflora is beginning to be discerned. For example, it was recently shown that the recognition of commensal bacteria by epithelial cells protects against intestinal injury.2 Appropriate immune recognition of enteric bacteria is also essential to host–bacteria symbiosis, and a recent report by Mazmanian and colleagues implicates a single bacterial molecule as critical