A rough estimation based on bacteria-infecting viruses (bacteriophages) indicates that there are 100 times more viruses than eukaryotic cells in our body. Viruses affect the very foundation of our nature, our genome. Reminiscences of ancestral human-viral cohabitation are imprinted in our genome with approximately 100,000 known endogenous viral fragments, representing approximately 8% of our genome. The human virome in non-pathogenic conditions: distribution of the viral families found in the major human systems.Our goal is to better understand the human virome in relation to human health and disease using multiomics and deep learning.
The human microbiome represents vast potential for understanding issues of human health, ecology, and disease. Under the integrated human microbiome project (iHMP/HMPII), Dr. White III lead metaproteomics data collection, analysis and investigation in an HMPII project called onset of Inflammatory Bowel Disease (IBD). It’s part of a massive multi-omics investigation of Crohn's disease (CD) and ulcerative colitis (UC), and includes data from healthy controls (HC) (https://www.ibdmdb.org/project/). Our combined multi-omics manuscript is currently in review in Nature (Lloyd-Price, White 3rd et al., 2019), and represents the most extensive data collection of omics related to IBD. Highlights of metaproteomic data only (White 3rd in prep), include higher protein expression rates in phage integrases and portal proteins in CD patients compared to HC. At the same time, UC patients have enriched coliphage protein expression compared to the healthy controls. My recent collaboration with Nanjing Medical University, China (Dong, White 3rd et al., 2018, Clin Transl Gastroenterol), found a correlation between the microbiome of meconium (that is, an infant’s first feces) and the development of neonatal jaundice, which affects 60% of all newborns. Bifidobacterium pseudolongum in newborn meconium was higher in relative abundance (based on 16S rDNA amplicon sequencing) and was significantly associated with a lower risk of jaundice in both cesarean-born infants and in the total number of subjects. My earlier work on phage represented the first virome (viral microbiome) of human saliva (Pride, White 3rd et al., 2011, ISMEJ). The work also suggested a distinct viral community in saliva compared to stool and the respiratory tract, and that phage could be a potential reservoir for bacterial virulence factors.
The interaction of the gut with the oral microbiome promises interesting discoveries for interactions between a host and its environment. The oral microbiome represents a simplified community, whereas the gut represents a highly complex microbial community. Together, they provide a system by which to model microbial complexity at each extreme of the scale. First, digestion involves saliva with the final absorption of nutrients that enter the gut. These gut microbiomes are the "training wheels" of the human immune system, and a hotbed of host-bacterial-phage interactions. Phage regulate bacterial abundance, gene exchange, and they potentially encode genes acting as virulence factors or serving useful accessory functions. Little is known about the phage effect on the human microbiome. Our work will explore beyond 16S amplicons, and get into the functions and end products of metabolism from these host-bacterial-phage interactions by using multi-omics, computation, and modeling. With a combination of animal, synthetic-built microbiota (simplified bacteria isolated from culture collection), and patient samples my work will will explore hypotheses relating to phage-free microbiomes.