Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut

Abstract

The virome is comprised of endogenous retroviruses, eukaryotic viruses, and bacteriophages and is increasingly being recognized as an essential part of the human microbiome. The human virome is associated with Type-1 diabetes (T1D), Type-2 diabetes (T2D), Inflammatory Bowel Disease (IBD), Human Immunodeficiency Virus (HIV) infection, and cancer. Increasing evidence also supports trans-kingdom interactions of viruses with bacteria, small eukaryotes and host in disease progression. The present review focuses on virus ecology and biology and how this translates mostly to human gut virome research. Current challenges in the field and how the development of bioinformatic tools and controls are aiding to overcome some of these challenges are also discussed. Finally, the present review also focuses on how human gut virome research could result in translational and clinical studies that may facilitate the development of therapeutic approaches.

Keywords: microbiome; phage therapy; viral mock communities; virome.

Figure 1

Flow gram of potential applications of high-throughput sequencing in the discovery of an unexpected eukaryotic virus in a disease, and the discovery of eukaryotic viruses in a disease of unknown etiology.

Figure 2

Potential phage-mediated lysis of commensal and pathogenic bacteria in the human gut. Panel (A) shows lysis of commensal bacteria in the human gut triggered by external factors that would need to individually be evaluated for each disease phenotype (e.g., Type 1 diabetes (T1D), Inflammatory Bowel Disease (IBD) and cancer). Panel (B) shows how phages can potentially aid in pathogen lysis. This is hypothesized based on T4 phages in vitro experiments [36].

Figure 3

Lysogenic conversion of commensal bacteria. Temperate phages can carry genes that can confer an evolutionary advantage to the bacterial host cell. Figure shows antibiotic-resistance as an example, which can further aid commensal bacteria to survive when exposed to specific antibiotics.

Figure 4

Phages as potential human pathogens. This was probably first suggested with phages harboring stx, which represents a serious risk to human health. Stx B subunit targets a human endothelial cells receptor known as Gb3. Another study involving introducing phages infecting bacteria from the Enterobacteriaceae, Staphylococcaceae and Streptococcaceae families to mice also demonstrated the possibility of phages as human pathogens. An increase in lactulose/mannitol ratio and in Butyrivibrio, Oscillospira and Ruminococcus relative abundances, as well as a decrease in Blautia, Catenibacterium, Lactobacillus and Faecalibacterium relative abundances was observed. The decrease in Lactobacillus and Faecalibacterium (highlighted in red asterisks), specifically, is associated with impaired gut permeability and inflammation.