About the Study
Type 2 diabetes mellitus (T2D) is a significant health problem facing our nation and our study is likely to provide important insights into this disease. Close to 20 million individuals in the United States have T2D, which cost $174 billion in 2007 to treat, a figure projected to double by 2050. Currently, there are an estimated 79M prediabetics in the United States who have a lifetime risk of diabetes conversion of 50%.
Differences in the gut microbiome have been noted between diabetics and healthy individuals, and direct alteration of the microbiome in mice has been shown to lower glucose levels. To better understand the biological changes that occur T2D disease acquisition, we plan to perform a detailed analysis of the biological processes that occur in patients at risk for T2D and their microbiomes by longitudinal profiling of patients during healthy periods and periods of stress.
The Study Will...
- Establish a cohort of approximately 100 consented individuals at risk for diabetes. Samples will be taken frequently (at 1-to-4-day intervals) during infected and other stress states and less frequently (every ~3 months) during healthy periods, with a minimum of 27 timepoints sampled per subject.
- Perform omics analysis of longitudinal patient samples and samples of their microbiomes. Microbiome genetic, transcriptome, and proteome content will be determined in fecal and nasal samples (for viral and endogenous microbiome populations). Patient genomic, transcriptomic, and proteomic data will be concurrently analyzed from blood (PBMCs for genome and transcriptome; plasma for proteome). Combined patient and microbiome metabolites will be analyzed in serum and urine. Anti-virome antibodies will also be analyzed.
- Analyze and integrate patient data and microbiome data. The different viral and fecal microbiome data (genome, transcriptome, and proteome) will be analyzed individually and in a combined fashion to determine the dynamic pathways that change during viral infection. In addition, we will correlate microbiome data temporal profiles with those of the patients to obtain an unprecedented view of the global microbiome-host changes that occur during viral infections.
Overall, our longitudinal study is expected to reveal global changes in the microbiome of patients at an unprecedented level of detail, and allow us to identify the molecules and pathways that change during viral infections and during diabetic onset and progression.