Necrotizing Enterocolitis (NEC) is a life-threatening illness that primarily affects preterm newborns. It starts suddenly a few days after birth, and leads to a high mortality rate. The treatment mainly relies on medical actions (antibiotics, fasting) and sometimes surgery. The rapidity of aggravation implies a strong need for early – and even predictive – diagnosis. Faced with the limits of current diagnosis, omics-based approaches have been proposed. Among these approaches, volatolomics, which focuses on the study of volatile organic compounds (VOCs) emitted from cells and their microenvironments, has proven to be relevant to reveal changes in response to physiological disorders induced by pathologies or xenobiotic exposures.

The present study aims to investigate the potential of fecal volatolomics to reveal early NEC-related metabolic disturbances in preterm newborns. This study is based on a cohort of 216 preterm newborns formed by the Clermont-Ferrand University Hospital (France). Stool samples were collected during the first month of life. Three newborns with a severe NEC were matched with 8 healthy controls. To comprehensively characterize fecal volatolome, we implemented solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS), taking care to preserve volatolome information throughout the workflow by immediately freezing collected samples and extracting VOCs at a temperature no higher than body temperature. More than 280 compounds were monitored from the birth of newborns until the day of NEC diagnosis. Comparison of volatolomes of NEC and control samples pointed out NEC-related metabolic disturbances, with up to more than 70 VOCs significantly modified (p < 0.01). The performance of diagnosis models based on candidate VOCs markers was assessed. Use of VOC markers is very promising for early NEC diagnosis in preterm newborns.