Innate Immune Influences on the Gut Microbiome: Lessons from Mouse Models

The gut microbiota is important in health and disease. Whereas the intestinal immune system has evolved to protect the mucosal barrier against pathogens, there is much interest in understanding how it influences the composition and functions of resident microbial communities. Overall, host innate immunity exerts little influence on the microbiota at homeostasis, but increases upon immune activation and the onset of inflammation, as well as in the presence of certain members of the microbiota. However, many experiments have not adequately incorporated study design to detect such immune influences, including using proper control groups, precise sampling and timing, and measures beyond broad-scale descriptions of dysbiosis for microbial analysis. We discuss these and other challenges in the context of current understanding of chronic inflammatory disease. Intestinal health (homeostasis) is maintained via mutualistic host–microbe symbiosis. The gut microbiota is known to be important for normal physiology and has been implicated in the pathogenesis of various inflammatory diseases such as Crohn’s disease and ulcerative colitis. In experiments that properly control microbiota, there is little evidence that the innate immune system influences the composition or functions of the gut microbiota under homeostatic conditions. Transient changes in the microbiota associated with inflammation may be indirectly influenced by redundant immune functions. Disease phenotypes may be influenced by the presence of specific bacteria within the microbiota. There are numerous challenges in interpreting immune influence on the microbiota: poor study design to isolate specific genetic influences; insufficient understanding of the microbiota due to inability to culture; and lags in technology.