Metagenomic characterisation of the gastrointestinal virome of neonatal pigs

Microorganisms that colonise the gastrointestinal tract are responsible for a large portion of the genetic diversity of the body. These microorganisms are of bacterial, archaeal and viral origin. The living space of these microorganisms, the microbiome, holds numerous interactions both between each other and the host. The viral part of the microbiome, the virome, consists of a multitude of virus species. These viruses infect and modulate cells from all three domains of life. Even though viruses have been acknowledged for their abilities to induce disease in its host, knowledge about the total diversity of viruses within the virome, and the role it plays in health and disease, is so far scarce. It is thought that the virome co-evolved with the host and that its establishment in mammals occurs early in life. The virome can be studied by the use of viral metagenomics, the study of all viral genetic material within a sample. Viral metagenomics was used in this thesis to generate datasets for comparative metagenomics. These datasets were then used for disease investigation and to compare similarities in the viromes of two mammalian species, pigs and humans. This thesis establishes a methodological framework for studying the virome in mammals, by use of viral metagenomics. A methodology for amplifying the metagenome prior to sequencing was assessed and a software for bioinformatics analysis of viral metagenomes was developed. With the methodologies developed herein, the eukaryotic virome of neonatal piglets suffering from diarrhoea was investigated. Several known enteric viruses were detected using viral metagenomics on healthy and diarrhoeic neonatal piglets. However, no virus was present exclusively within sick or healthy piglets and no virologial cause could be established for the neonatal diarrhoea. Comparative viral metagenomics was also used to establish if similarities existed between neonates of porcine and human origin, as well as between adults and neonates. Similarities were detected between adults of both species, who seems to be sharing a considerable part of their virome. There was also a notable difference between neonatal viromes and adult viromes, further supporting established theories about diversification over time of the virome.