Shifts in microbial transcription patterns prior to onset of Necrotizing enterocolitis may indicate low oxygen levels in the gut

Summary Premature infants are at risk for developing necrotizing enterocolitis (NEC), an inflammatory disease that can progress to necrosis of gut tissue. Previous attempts have failed to identify any consistent predictor of NEC. We hypothesized that prior to the appearance of NEC symptoms, the gut microbiome shifts in its transcriptional profile. To test this hypothesis we integrated genome-resolved metagenomic and metatranscriptomic data from multiple time-points in the first month of life of four preterm infants, two of whom later developed NEC. Gut microbiomes of NEC infants showed increased transcription of high oxygen affinity cytochrome oxidases and lower transcription of genes to detoxify nitric oxide, an antimicrobial compound released by host cells. These results, and high transcription of H 2 production genes, suggest low O 2 conditions prior to NEC onset, and are consistent with hypoxic conditions in diseased gut tissue. The findings motivate further testing of transcript data as a predictor of NEC. Highlights Transcription of high oxygen affinity microbial cytochrome oxidase may predict necrotizing enterocolitis (NEC) development. Lower transcription of microbial genes to detoxify nitric oxide (NO) may also predict NEC development. Higher transcription of H 2 production genes by Escherichia sp. was found in the gut of premature infants that develop NEC.