Aging-associated modification of intestinal homeostasis and barrier function: Role of microbiota, iNOS and innate immunity

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Results of several studies suggest that intestinal microbiota and barrier function may majorly impact health maintenance and longevity thereby also modulating healthy life-span. Furthermore, impairments of intestinal barrier function, changes in intestinal microbiota composition and alterations of the TH1/TH2 cell balance as well as redox status in the gut are discussed to be critical in the development of the low-grade inflammation frequently found in elderly. We recently found that old age in mice is associated with changes of intestinal microbiota composition and impairments of intestinal barrier function which went alongwith decreased expression levels of iNOS and proinflammatory mediators in the upper parts of the small intestine. However, the interaction between intestinal microbiota, barrier function, immune system and aging-associated degeneration and decline is only partially understood. Starting from this background, using mouse models the aim of the present research project is (1) to delineate at what age modifications of intestinal homeostasis and barrier function set in and if these changes are associated with alterations of intestinal microbiota composition and NO bioavailability as well as TH1 cells prevalence in small and large intestinal tissue, and (2) to determine the role of NO-synthesis through iNOS in aging-associated modifications of intestinal microbiota composition and barrier function. Herein, we will especially focus on the role of dietary composition and energy bioavailability as well as the identification of novel targeting strategies to prevent aging-associated alterations of intestinal microbiota composition and barrier function. We thereby also aim to add to the understanding of the fundamental principles of microbe-host interaction.