PROJECT SUMMARY The gut microbiome has a profound effect on human health by influencing the development of the immune system, producing bioactive metabolites and directly aiding in the processing of food. Changes in the composition and metabolism of the gut microbial community has been associated with a wide array of human diseases, including malnutrition, auto-immunity, and even neurological function. A central aspiration of gut microbiome research is to identify individuals with abnormalities in gut microbial composition in order to intervene therapeutically. However, a major limitation is that it is logistically challenging to evaluate gut microbial composition in a patient-care setting. The studies in this proposal will advance a novel strategy to overcome this roadblock. Based on powerful preliminary studies in germ-free mice and in humans, our central hypothesis is that the volatile composition of breath offers a dynamic representation of the composition and function of the gut microbiota. We will test this hypothesis by evaluating the association between breath, gut bacterial species, and microbial metabolic functions (Aim 1). In addition, we will use two unique clinical cohorts of infants to determine how the breath volatile profile changes dynamically with changes in gut microbial community composition (Aim 2). Together, our studies will not only advance our fundamental understanding of the spectrum of breath volatiles that arise from microbial metabolism, but will also be a critical first step in determining how “breathalyzer” diagnostics of gut health can be applied clinically.

PROJECT NARRATIVE The gut microbiome affects multiple aspects of human health and has been causally linked to a wide range of medically important conditions including cancer, heart disease, chronic lung diseases, and autoimmunity. Despite our advance in understanding the mechanism by which the gut microbiome causes disease, there is no straightforward clinical diagnostic test to measure “gut health.” Our proposal is highly relevant to public health because it will advance a new strategy to aid development of a non-invasive breath-based readout of the gut microbiome.