Project 171447

The human gut is densely colonized with microbes. We have evolved over time with these microbes, and it appears that we not only tolerate these organisms, but our immune system and gut requires them for proper development and health. Lactobacillus and Bifidobacterium strains are found in the human gut and have the ability to regulate immune function. Strains of Lactobacillus and Bifidobacteria are commonly used as probiotics, which are defined by the World Health Organization as live microorganisms that when administered in adequate amounts, confer a health benefit on the host. Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions of the gut whose cause remains unknown. In patients with these diseases, their immune system appears to be responding inappropriately to normal non-pathogenic bacteria in the gut. The focus of this grant proposal is to isolate bioactive factors that are released from certain strains of probiotic bacteria and to test their ability to prevent the onset of inflammatory bowel disease in mice that are genetically programmed to be susceptible to developing colitis. Further, we will determine if treating mice with probiotics either during the prenatal period or from birth will decrease their risk of developing inflammatory bowel disease in later life. The goal of this research is to develop treatments based on probiotics and their products that can be used both to treat patients with Crohn's disease and ulcerative colitis, and to prevent disease occurrence in children that are at high risk of developing the disease because of their genetic background.

investigating the potential of probiotics and their bioactive factors to prevent inflammatory bowel disease in a genetically susceptible mouse model, including prenatal and early life interventions