U.S. Department of Health and Human Services

Early Exposure to “Friendly” Microbes Protects Against Inflammatory Bowel Disease (IBD) and Asthma

Diseases such as IBD and asthma are believed to occur, in part, because of inappropriate immune responses to “friendly” bacteria. However, exposure early in life to these bacteria appears to modify disease responses. In a study designed to explain these apparent contradictions, scientists have used mouse models to detect the relationships of microbes and immune cells to IBD and asthma. The scientists began their study by looking for pro-inflammatory cells called iNKT (invariant natural killer T) cells in tissues that line the intestines and lungs of mice. These iNKT cells have been associated with inflammation related to ulcerative colitis (UC), a major form of IBD, and asthma. A greater number of iNKT cells were seen specifically in the intestinal linings and lungs of mice that were raised in germ-free conditions (GF mice) compared to mice that were raised in an environment of “friendly” bacteria, SPF (specific pathogen-free) mice. Also, the high number of iNKT cells was observed to remain constant for life. All of the study mice were given a chemical substance that mimics UC by inducing inflammatory symptoms. The GF mice responded with far greater sensitivity to UC induction, suffering severe weight loss and higher death rates compared to the SPF mice. To see if inflammation could be prevented in adult GF mice, the adult mice were introduced to “friendly” bacteria before UC induction, but this had no effect on disease development. However, when pregnant mice were exposed to “friendly” bacteria shortly before delivery, the offspring were protected against UC induction, confirming that protection against UC is a time-sensitive phenomenon that is acquired in the presence of “friendly” bacteria early in life. 

This type of protection was also demonstrated in a mouse model of asthma. CXCL16 is a pro-inflammatory protein that regulates iNKT cells. In their search for a mechanism underlying susceptibility to UC and asthma, the scientists analyzed the concentration of CXCL16 in samples of mouse blood. The analysis revealed that concentrations of CXCL16, as well as iNKT cells, were significantly elevated in GF mice compared with SPF mice, and that iNKT cells were reduced in the intestines and lungs of mice when CXCL16 interaction with iNKT cells were blocked by antibody interference. Scientists have shown with this study that very early exposure to “friendly” bacteria is necessary to protect against inflammatory responses associated with UC and asthma in mice, and that this protection is enduring. Also, the mechanism for disease sensitivity is dependent on CXCL16 stimulation of iNKT cell inflammatory responses. Although this study was conducted in mice, the mouse system explored and its human counterpart are very similar, and it is expected that these findings will be relevant to developing new treatments for UC and asthma in humans.

Olszak T, An D, Zeissig S, et al. Microbial exposure during early life has persistent effects on natural killer Tcell function. Science 336:489-493, 2012.​