Project Summary Chronic inflammation is common in developed countries and is associated with the development of cancer, heart disease, and diabetes. Chronic inflammation is caused by immune dysregulation and has been linked to dysbiotic, low diversity gut microbiotas. Dietary intervention has shown promise in the treatment of these disorders, but the mechanisms underlying this effect are unclear and which type of foods will be effective are under debate. This project leverages collected samples and data from a recently conducted fermented food (yogurt, sauerkraut, kimchi, etc.) dietary intervention study in healthy adults, in which inflammatory markers decreased over the course of the intervention. Here, I will perform high resolution metagenomic, metabolomic, and immune profiling on fecal and blood samples from this study to better understand the extent and basis of fermented foods impacting the human immune system and endogenous microbiome (Aim 1), and additionally perform a series of highly-controlled mouse experiments to determine the specific components of fermented foods that are responsible for immune modulating effects (Aim 2). My previous experience in computational biology and bioinformatics make me well-equipped to analyze the large amount of data that will be generated, and the expertise in animal models for microbiome analysis, immunological profiling, and metabolomic analysis honed by my mentoring team make Stanford University an ideal location to learn the skills I will need to perform the technical experiments. Completion of these aims will generate a detailed understanding of the effects that fermented foods have on the mammalian immune system and endogenous microbiome, identify specific microbial strains and metabolites associated with decreased inflammation in humans, and establish the specific components of fermented foods that improve immune system regulation, paving the way for evidence-based guidance on the consumption of fermented foods and the development of precision therapeutics to reduce chronic inflammation and prevent acute disease.