Immunologic imbalances underlie many human diseases. Food allergies represent serious disorders whereby the immune system reacts inappropriately to otherwise innocuous ingested molecules. In addition to the medical and social burden of severe reactions such as anaphylaxis, the incidences of food allergies are alarmingly increasing in Western societies. The hygiene hypothesis proposed two decades ago speculated that increases in allergic diseases are the result of lifestyle changes that reduce exposure to microbes. Microbial infections are, in fact, rare and opportunistic. In contrast, mammals are colonized for life with 100 trillion commensal bacteria, and the contributions of beneficial microbes to human health appear to be profound. Studies in animals show that gut bacteria are an important component for the development of oral tolerance, as germ-free mice display deficits in controlling immune reactions to food antigens. Intriguingly, people with allergies in developed countries have alterations in the community composition of their gut microbiota. Therefore, societal advances (including vaccination, sanitation, 'western'diets, and anti-bacterial therapeutics) may have paradoxically affected human health adversely by reducing our exposure to health-promoting bacteria. We have identified and characterized a beneficial human microbe with the profound function of inducing antigen-specific tolerance. We propose to investigate the innovative hypothesis that a symbiotic gut bacterium can correct the immune imbalances in experimental models of food allergy. Furthermore, we will examine the cellular mechanism(s) required for protection from disease. These seminal studies may lead to the development of novel therapies to food allergies based on harnessing the immune-modulating properties of symbiotic gut bacteria. Food allergies are serious medical disorders caused by uncontrolled immune reactions to dietary antigens, which result in severe medical outcomes. As there are currently no viable treatments, we seek to explore the potential of generating antigen-specific oral tolerance by inducing immune regulation as a novel therapeutic approach for food allergies.
Relevance: Food allergies are serious medical disorders caused by uncontrolled immune reactions to dietary antigens, which result in severe medical outcomes. As there are currently no viable treatments, we seek to explore the potential of generating antigen-specific oral tolerance by inducing immune regulation as a novel therapeutic approach for food allergies.
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