The gut microbiota shapes the human and murine breath volatilome

The gut microbiota is crucial to health, yet implementation of microbiota-based therapeutics is limited by the lack of rapid diagnostics. We hypothesize that breath contains gut microbe-derived volatile organic compounds (VOCs) reflecting microbiota composition and metabolism. In healthy children, we found that breath VOC composition (or volatilome), assessed by gas chromatography-mass spectrometry, correlates with gut microbiome composition and function. By capturing exhaled breath from human-stool-colonized and monocolonized gnotobiotic mice, we profiled breath VOCs and discovered that murine breath is also significantly influenced by the gut microbiome. VOCs from cultured gut microbes were identified in vivo in monocolonized gnotobiotic colonized mice. As a proof of principle, we demonstrated that exhaled breath predicts the abundance of a disease-associated bacterium, Eubacterium siraeum, in children with asthma. Altogether, our studies identify microbe-derived VOCs in breath, show that gut bacterial metabolism directly contributes to mammalian breath VOC profiles, and inform the development of non-invasive microbiome diagnostics.