Metagenomic Sequencing Identified Specific Bacteriophage Signature Discriminating between Healthy and Diarrheal Neonatal Piglets

Neonatal diarrhea is one of the most severe diseases in human beings and pigs, leading to high mortality and growth faltering. Gut microbiome-related studies mostly focus on the relationship between bacteria and neonatal diarrhea onset, and no research study has investigated the role of the gut virome in neonatal diarrhea. Here, using metagenomic sequencing, we characterized the fecal viral community of diarrheal and healthy neonatal piglets. We found that the viral community of diarrheal piglets showed higher individual heterogeneity and elevated abundance of Myoviridae. By predicting the bacterial host of the identified viral genomes, phages infecting Proteobacteria, especially E. coli, were the dominant taxa in neonatal diarrheal piglets. Consistent with this, the antibiotic resistance gene of E. coli origin was also enriched in neonatal diarrheal piglets. Finally, we established a random forest model to accurately discriminate between neonatal diarrheal piglets and healthy controls and identified genus E. coli- and genus listeria-infecting bacteriophages, including psa and C5 viruses, as key biomarkers. In conclusion, we provide the first glance of viral community and function characteristics in diarrheal and healthy neonatal piglets. These findings expand our understanding of the relationship among phages, bacteria and diarrhea, and may facilitate the development of therapeutics for the prevention and treatment of neonatal diarrhea.

Automated summary

Neonatal diarrhea is a severe disease in humans and pigs, but the role of gut virome has not been studied. Using metagenomic sequencing, the viral community of diarrheal and healthy neonatal piglets was characterized. The viral community of diarrheal piglets showed higher heterogeneity and elevated abundance of Myoviridae. Phages infecting Proteobacteria, especially E. coli, were dominant in neonatal diarrheal piglets. Genus E. coli- and genus listeria-infecting bacteriophages were identified as key biomarkers for discriminating between neonatal diarrheal piglets and healthy controls. These findings expand our understanding of the relationship among phages, bacteria, and diarrhea, and may aid in the development of therapeutics for neonatal diarrhea prevention and treatment.