Our viral companions (column)
Some of you may have attended the free public forum on “Little Guys, Big Jobs: Microbes at Work in Your Body” hosted by Keystone Symposia on Molecular and Cellular Biology on March 3. The event featured three leading experts on the human microbiome who discussed the microorganisms that live in, and on, our bodies. They addressed topics ranging from the characteristics of bacteria in our gut to the pros and cons of dietary probiotics. The speakers noted that the human gut hosts trillions of bacteria that aid digestion, produce nutrients and vitamins, influence the immune system, and displace pathogens.
One topic touched on was that of the human virome: the collection of all viruses that call the human body home. Most people think of viruses as exclusively causing specific diseases, such as the flu or Ebola, and don’t realize that we are riddled with viruses or viral remnants that generally cause us no harm. For example, recent studies suggest that 8 percent of our genome is derived from viruses, much of it the remnants of ancient viruses that are essentially dead. Furthermore, we are all infected with multiple viruses that persist in a dormant or semi-dormant state our entire lives. For example, virtually all of us are chronically infected with one or more of the eight human herpes viruses, such as the chicken pox virus that can cause chicken pox and shingles, the Epstein-Barr virus that can cause mononucleosis, and the Cytomegalovirus that can cause disease in neonates and the immunocompromised. After the disease caused by the initial viral infection ends, the virus can persist for life with minimal impact (although individuals who have suffered from reactivation of the chicken pox virus and the resulting shingles might disagree with this statement).
Viruses also play a significant role in our digestive tracts. In fact, the collection of viruses that inhabit our guts is even more diverse than our bacterial microbiome. Interestingly, many viruses in our bodies are bacteriophages — viruses that infect bacteria but not human cells. There are approximately 100 bacteriophages for every bacterium in your body. This is an incredible amount considering that we all harbor approximately 1014 (100 trillion) bacteria. These bacteriophages constantly infect and kill host bacteria in a balance with bacterial growth and resistance, thereby regulating bacterial density. This dynamic equilibrium is illustrated by studies in the horse gut where it has been shown that a class of bacteriophages called coliphages regulates the diversity and abundance of Escherichia coli bacteria.
Since bacteriophages infect and kill bacteria, they have a huge impact on the probiotics many of us ingest. In fact, some probiotics may not elicit long-lasting effects due to the natural selection of phages specifically infecting the ingested probiotic strains, and probiotic efficacy may quickly decline with regular use. Consistent with this idea, recent genome sequencing studies have revealed that many common probiotic bacterial strains are targets of bacteriophage predation. While this may seem problematic for the probiotic industry, it is also an opportunity for a different approach to modifying our gut microbiomes. Indeed, there is growing interest in regulating the bacterial microbiome, not by ingesting more bacteria, but by ingesting selected populations of bacteriophages. The approach leverages the fact that bacteriophages have potent antibacterial activity, but in contrast to antibiotics, are very specific; i.e., they only kill targeted bacterial species. This specificity means that bacteriophage-based probiotics can be developed that lack the deleterious effects on beneficial gut microflora. The idea may seem far-fetched, but already the Bill & Melinda Gates Foundation is encouraging research by seeking visionary grant applications to develop bacteriophage-based approaches to improve gut health. Bacteriophages might also be adopted by the livestock industry. A recent comparison of probiotics and bacteriophages in pigs revealed that whereas both improve different aspects of pig health, bacteriophages are more effective than probiotics, and both are preferable to the current use of antibiotics. Antibiotics also change the composition of gut microbiota but act as sledgehammers, killing many bacteria and modifying the microbiome in unhealthy ways.
So the next probiotic that you take may be teeming with viruses. In the meantime, I’ll stick to my yogurt and contemplate the fact that my genome harbors way more viral sequences than my laptop!
David L. “Woody” Woodland, Ph.D. is the chief scientific officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at 970-262-1230 ext. 131 or firstname.lastname@example.org.
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