Project Summary - Abstract. The human immune system has many different pathways that regulate the susceptibility to disease. Recent studies, such as Dopico et al. (2014), have shown that the gene expression in the immune system varies by season, suggesting that immunity and disease susceptibility may be seasonally structured. Along with the seasonal change of the immune system, the microbiome has shown seasonal influence. These two elements combined create an enhanced avenue to investigate infectious disease transmission and immunity. Our proposed project consists of two parts. First, we will test the hypothesis that the human gut microbiome changes with the seasons (in humans living in a modern urban environment). We will do so using biobanked samples collected for the parent DP5 grant project. Microbial DNA will be extracted, amplified, and sequenced from stool samples from study participants sampled winter, spring, summer, and fall 2019. Second, we will investigate whether cytokine production by the immune system is seasonally modulated. We focus on cytokines because they have the potential to feedback with gut microbiota. Cytokine assays will be run using live immune cells that were also collected seasonally from study participants and preserved in our biobank. Variation in the gut microbiome and cytokine response will be analyzed within-individuals across seasons and compared between-individuals. Collectively, the data produced by this supplemental project will further understanding of seasonal biological cycles with direct implications for clinical medicine and public health. Lastly, knowledge of seasonal structuring within the human body may further our knowledge of why infectious diseases are seasonal.