The Virome and How It Makes You Unique
Change the Skin I’m In: Human Virome and Epigenetics
When most of us think of changing our skin, we think of altering our daily regimen or trying out a new cream/lotion. What we often don’t think about are the small microorganisms (such as bacteria, fungi, and viruses) that inhabit our body. Viruses specifically can affect our skin through not only infecting our skin cells but also changing the characteristics of the microorganisms that live on us, such as bacteria and fungi. These viruses living among us are known as the “virome.”
Many people know that healthy humans have a diverse microbiome, but healthy humans also colonize a healthy level of viruses known as the virome. The composition of the human virome includes viruses that infect human cells, ancient virus-derived elements inserted in our chromosomes, and bacteriophages that infect a broad array of bacteria that inhabit us.
Viruses are microscopic, infectious parasites that can only reproduce through host cells. They are also the most abundant and most diverse biological entity of the biosphere. They can cause disease and comprise of a core RNA or DNA surrounded by a protein coating. Many studies of the skin have investigated the bacterial and fungal communities living on the skin, but few studies have analyzed how viruses and their infections have played a role in developing disease.
How Does the Virome Affect Human Genetics?
Viruses have the special ability to invade a cell, whether it is a bacterial or human cell and direct the cell’s machinery to replicate the virus. Most viruses contain either DNA or RNA with a single or double stranded nucleic acid. This genetic material can encode proteins by either utilizing cellular enzymes or ribosomes.
Humans have been influenced by viruses for centuries. Eight percent of our DNA consists of remnants of ancient viruses, and another 40 percent is made up of repetitive strings of genetic letters that are also thought to have a viral origin. The virome lends another opportunity for viruses to insert into cells and make changes to our DNA. Recently, the virome has been recently linked to the development of autoimmune conditions. The more we learn about the virome and its ability to insert and change our DNA, the better we can understand these conditions.
What Influences the Virome Composition?
Like bacteria, viruses and viromes change depending on their environment, whether on the body or in the household. In a study that compared the viruses present in saliva, respiratory tract, and stool, each location had distinct viromes. The study also showed that the most abundant virus present in the oral biome was bacteriophages. Bacteriophages are viruses that can infect and kill bacteria without any negative effect on human or animal cells.
Recent studies have shown that associations exist between the virome and factors such as diet, age, and geographic location of an individual. Disease is another prominent influence, with emerging studies suggesting associations between virome structure and inflammatory bowel disease, diabetes, hypertension, and cancer.
The Virome in Healthy Humans
As more interest in the virome grows, more studies have investigated the composition of the virome in healthy humans. A study was conducted involving 706 samples from 102 subjects. The samples were taken from five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats.
This study detected about 5 viral genera which included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each participant had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. This study highlights the diversity of the genome and gives insight regarding which viruses are present in our virome.
The Virome and Skin
The human virome is complex and has an influence on many disease states. Many viruses have been shown to modulate and alter cutaneous health. Bacteriophages in particular, have been shown to influence the skin’s microbial community through predation. This makes it a favorable choice to target skin bacteria such as Propionibacterium acnes.
Propionibacterium acnes is a Gram-positive rod-shaped bacterium found on the skin; it represents nearly 90% of the skin microbiome of healthy adults. One of the therapies for P. Acnes includes antibiotic therapy, but as more antibiotics are prescribed, resistance grows.[4,5] Therefore, scientists wanted to explore the relationship with bacteriophages as a potential therapy.
P. Acnes Bacteriophages
As mentioned before, Bacteriophages are viruses that infect bacteria and play an important regulatory role in skin. They can bind to the bacterial receptor, inject their DNA, and induce bacterial lysis. With increasing antibiotic resistance, bacteriophages have become a topic of interest. They can break down bad bacteria without becoming resistant. With increasing resistance to bacteria like Pseudomonas and Staph, this offers exciting possibilities. So far only two clinical trials have been well executed to show that phage therapy is beneficial against venous ulcers and chronic otitis media.
Some research has been done to explore bacteriophage’s role in acne treatment. Bacteriophages active against P. acnes have been isolated from the skin, oral cavity, and gastrointestinal tract which means our own virome has viruses that can lyse P. acnes. Although, the therapeutic effects are yet to be studied in humans, this opens the possibility to using bacteriophages in therapies targeting the breakdown of P.acnes. The concern is that due to its ability to exchange virulence and pathogenicity to the bacteria, there is a risk of transferring antibiotic resistance. That means that some of the current therapies against acne which include topical and oral antibiotics may become resistant. Therefore, the isolated bacteriophages incorporated into therapy should only have lytic therapy and be unable to transfer resistance.
Bacteriophage therapy has been used in humans for several types of infections with good results, however, no trials on P. acnes bacteriophage therapy have been conducted in humans.
The human virome is a collection of viruses that colonize in the body. The virome is an exciting area of research continuously being studied. The virome is thought to influence many disease states and one certain type of virus, bacteriophages, for its activity in bacterial lysis. The limitations include the possibility of a bacteriophage mutating a bacteria’s DNA making it resistant to conventional antibiotic therapies. If this hurdle can be addressed, these bacteriophages could offer possible treatments targeting harmful bacteria on the skin microbiome.
- Zou S, Caler L, Colombini-Hatch S, et al. Research on the human virome: where are we and what is next. Microbiome.2016;4(1):32; PMID: 27341799 https://www.ncbi.nlm.nih.gov/pubmed/27341799.
- Robles-Sikisaka R, Ly M, Boehm T, et al. Association between living environment and human oral viral ecology. Isme j.2013;7(9):1710-1724; PMID: 23598790 https://www.ncbi.nlm.nih.gov/pubmed/23598790.
- Pride DT, Salzman J, Haynes M, et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. Isme j.2012;6(5):915-926; PMID: 22158393 https://www.ncbi.nlm.nih.gov/pubmed/22158393.
- Lekunberri I, Subirats J, Borrego CM, et al. Exploring the contribution of bacteriophages to antibiotic resistance. Environ Pollut.2017;220(Pt B):981-984; PMID: 27890586 https://www.ncbi.nlm.nih.gov/pubmed/27890586.
- Modi SR, Lee HH, Spina CS, et al. Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature.2013;499(7457):219-222; PMID: 23748443 https://www.ncbi.nlm.nih.gov/pubmed/23748443.
- Foulongne V, Sauvage V, Hebert C, et al. Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PLoS One.2012;7(6):e38499; PMID: 22723863 https://www.ncbi.nlm.nih.gov/pubmed/22723863.
- Oh J, Byrd AL, Deming C, et al. Biogeography and individuality shape function in the human skin metagenome. 2014;10.1038/nature13786PMID: https://www-ncbi-nlm-nih-gov.evms.idm.oclc.org/pmc/articles/PMC4185404/.
- Denesvre C, Dumarest M, Remy S, et al. Chicken skin virome analyzed by high-throughput sequencing shows a composition highly different from human skin. Virus Genes.2015;51(2):209-216; PMID: 26223320 https://www.ncbi.nlm.nih.gov/pubmed/26223320.
- Wylie, K. M., Mihindukulasuriya, K. A., Zhou, Y., Sodergren, E., Storch, G. A., & Weinstock, G. M. (2014). Metagenomic analysis of double-stranded DNA viruses in healthy adults. BMC biology, 12, 71. https://doi.org/10.1186/s12915-014-0071-7
- Communications Department. (2020, April 13). The non-human living inside of you. Cold Spring Harbor Laboratory. https://www.cshl.edu/the-non-human-living-inside-of-you/
- Zou, S., Caler, L., Colombini-Hatch, S. et al. Research on the human virome: where are we and what is next. Microbiome 4, 32 (2016). https://doi.org/10.1186/s40168-016-0177-y
- Principi, N. (2019). Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections. Frontiers. https://www.frontiersin.org/articles/10.3389/fphar.2019
- Rhoads, D. D., Wolcott, R. D., Kuskowski, M. A., Wolcott, B. M., Ward, L. S., and Sulakvelidze, A. (2009). Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. Wound Care18, 237–238, 240–233. doi: 10.12968/jowc.2009.18.6.42801