Advanced volatilome analysis for assessing gut microbial metabolism

The olfactory sense of “smell” has long been used to detect disease. Hippocrates from ancient Greece characterized the pungent stench of melena as early as the Age of Pericles, and later, the traditional Chinese and Arab physicians documented distinct urinary scents in diseases such as diabetes. In 1971, Nobel laureate Linus Pauling quantified volatile organic compounds (VOCs) from breath and urine samples with modern analytical tools, and launched a new era of volatile and smell research. Mass spectrometry‐based techniques have greatly driven biomedical research in the past decade, and have generated excitement in biomarker discovery, disease diagnosis, and effective public health monitoring. A group of largely untapped metabolites, however, is the easily accessible biological VOCs that can be detected from the headspace of many biological specimens. While incremental progress has been made in this field, sensitivity, selectivity, and broad coverage of volatile metabolites are still suffering from underdeveloped measurement technologies. Fecal odor, driven in large part by the gut microbiota, is established to change in the presence of gastrointestinal disorders. Understanding these changes could help to diagnose various diseases. Shifts in microbiota composition, or overt gut dysbiosis, is associated with metabolic dysregulation (e.g., obesity, inflammatory bowel disease), although a causal role into impaired metabolism requires validation. Compared with clinical analysis of other body fluids and biological specimens, VOC analysis from the headspace of feces for gut dysbiosis detection has the potential to save analysis time (from hours to minutes) and significant reduce costs otherwise incurred from expensive blood chemistry or genomic approaches. However, VOC‐detection techniques are still far from reaching the maturity needed to widely support clinicians in making day‐to‐day patient care decisions. To address these critical needs, we developed and applied an innovative biological VOC detection technology (i.e. Secondary Electrospray Ionization‐High Resolution Mass Spectrometry; SESI‐HRMS) to sensitively and specifically detect metabolic VOCs of gut microbial metabolism during gut dysbiosis. Further, validation will be supported using a green tea polyphenols (GTP) intervention in an in vitro gut model during the process of rescuing the gut dysbiosis with the support of GTP. The results of the in vitro study were further compared with our controlled animal studies demonstrating the benefit of GTP intervention on gut dysbiosis that otherwise occurring in obesity. Support or Funding Information This work is supported by The Ohio State University James Comprehensive Cancer Center, The Food for Health Initiative, and the NIGMS grant R35GM133510.