New test developed that rapidly profiles the human virome

Molecular representation of an antibody (green) binding with an HIV virus (red and yellow).

The viruses that live in our body may be just as important to our health and development as their bacterial counterparts.  Unfortunately, testing which ones currently exist, or have at point infected us is expensive, time consuming, and laborious using current techniques.  Making matters worse, these techniques, which usually rely on measuring the amount of antibodies against specific viruses that exist in our blood, are often times ineffective when the antibodies are in low levels.  Recently though, scientists from Harvard University developed a new technique that can accurately, rapidly, and inexpensively (~$25) screen for the existence of over 200 viral antibodies in less than a drop of blood.  They call their technique VirScan, and they published their method last week in Science.

The scientists combined two advanced biological screening tools to create their method: DNA microarray synthesis and phage display.  In short, the scientists created libraries of peptides that represented 206 known human viruses, like HIV and influenza, and expressed them on simple bacteriophages.  They then combined these bacteriophages with a drop of blood, which itself contains antibodies that combat viruses that someone currently has, or has been infected from in the past.  The antibodies that exist specifically bind to the phages that represent a virus.  They then eliminate all the phages not bound to antibodies, and measuring what remains gives the scientist an indication of which antibodies were in the blood.  This explanation of the researchers’ technique may not satisfy our more curious readers, so those that wish to learn more should definitely check out the paper. When the scientists screened over 500 people using this method, the results showed that most people tested positive on average for 10 viruses (i.e. they had antibodies against these viruses).  Interestingly, 2 individuals tested positive for 84/206 viruses.  The most commonly detected virus was Epstein-Barr virus, followed by types of rhinovirus (common cold), and adenovirus.  Also of interest was that the viral structures differed geographically between continents.

This assay has many immediate implications in many areas.  The most obvious is its use as a diagnostic tool for easily screening people for their viruses.  In addition though, by discovering which peptides antibodies efficiently bind to, and how those differ between humans, more effective vaccines can be developed that treat more people.  Also, it should be interesting to discover how infection with certain viruses influences long term health and chronic disease.  For example, were those two individuals that tested positive for antibodies against 84 viruses more, or less healthy than those who tested positive for very few, and whether infection with certain viruses is associated with any chronic conditions.

Episode 5 of The Microbiome Podcast: Diet and its impact on our microbiota and health with Drs. Erica and Justin Sonnenburg

As we read on yesterday's blog post, dietary fibers alter the microbiome. On this week's episode of The Microbiome Podcast we talked in depth with Drs. Erica and Justin Sonnenburg from Stanford University about dietary fibers and their impact on our microbiota and our health.  Erica and Justin wrote a book that was published today called The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-term Health. You can buy it here on Amazon and it's a highly recommended read for anyone interested in the microbiome. 

Check out the newest episode on iTunes, Stitcher, or listen on our website. 

We will continue answering your questions on the podcast so please call 518-945-8583 with any questions for us or for next week's guest, Dr. Elaine Hsiao.

See below for more detailed show notes from today's episode: 

(1:17) Dr. Rob Knight received a Creative Promise in Biomedical Science Prize from the Vilcek Foundation. Read more.
(3:09) Rob Knight also published a book called Follow Your Gut: The Enormous Impact of Tiny Microbes. Click here to buy it on Amazon. 
(3:33) uBiome recently began a pregnancy microbiome study to better understand how the bacteria in our bodies change during and after pregnancy. Find out more on the uBiome website. 
(4:56) Microbiome Therapeutics performed a clinical study with an investigational drug in type 2 diabetics taking metformin and found that the drug resulted in more tolerability for patients and fewer side effects than metformin without the drug. Read more.  

In the (9:40) conversation with Erica and Justin Sonnenburg (read more about their research), we talked about several topics pertaining to diet and dietary fiber and its impact on our microbiota and health. We also discussed: 

(11:49) Why they decided to write the book.
(16:05) Their personal experiences having children and the importance of nurturing their health and its impact on their lives.
(17:55) Dietary fibers and differences among various types of fibers in our diets.
(26:15) How fast does diet change the microbiota?
(32:05) Bacteroides thetaiotaomicron and why it is Erica and Justin's favorite microbe and a study Justin published in 2005 while he was in Jeff Gordon's lab. Read the paper here.  
(37:35) How microbiome therapies are going to look in the future. 
(41:00) How eating better can make an impact now on our overall health. Read the seminal obesity and microbiome paper Erica mentions from the Gordon laboratory. 

We also answered two other (44:00) listener questions about phage therapy and organic vs. non-organic baby and adult foods. 

Next week we will be talking with Dr. Elaine Hsiao from Cal Tech so please call 518-945-8583 with your questions about autism and the microbiome as well as the microbiome's ability to regulate serotonin levels. 

Schizophrenia and the virome

Schizophrenia PET scan

Schizophrenia is a mental health disorder in which people cannot recognize reality, suffer from hallucinations, and experience social withdrawal.  The causes of schizophrenia are unknown, but it is thought to include genetic, environmental, psychological, and social risk factors.  As we have written about extensively in this blog, the bacteria and viruses in our body have an important connection to our brain and behavior, in what has been termed the ‘gut-brain axis’.  Considering the gut-brain axis, a team of scientists from Johns Hopkins University wondered if the microbiome, and specifically the virome, was somehow related schizophrenia.  They recently published their findings in Schizophrenia Bulletin.

The scientists sampled the throat microbiome from 74 people in the Baltimore, MD area, 41 of whom suffered from schizophrenia and 33 of whom did not.  They discovered that a specific bacteriophage (virus that infects bacteria), Lactobacillus phage phaidh, was linked to schizophrenia, which was found in 17 of the 41 schizophrenia patients, but only 1 of the 33 control individuals.  In addition, 9 of those 17 schizophrenics had a comorbid immune disorder, such as diabetes or Crohn’s disease, whereas only 2 of the remaining schizophrenics without the phage had these diseases.  The scientists also found a loose link between taking the drug valproate and occurrence of the phage.  Interestingly, this drug has been previously shown to affect the microbiome.  Finally, the existence of the phage coincided with higher levels of the bacteria that the phage attacks, Lactobacillus gasseri.  This is an unsurprising result because a phage and its target are usually found together.

The scientists acknowledge that the results of this study do not prove any real association between the microbiome and schizophrenia, but based on the results, they suggest that further research is warranted.  Notably, Lactobacillus gasseri is sometimes included in probiotics to supposedly relieve gastrointestinal issues.  However, if gasseri’s phaidh phage goes along with it, then according to this study, it may cause more harm than good.

The virome

Bacteriophages (bacterial viruses) attached to a bacterial cell wall.

A review in the journal Cell written by Herbert Virgin describes the exploration of the virome, a part of the overall microbiome which includes viruses, as an emerging study of importance in relation to human health. The size of the mammalian virome –viruses that infect mammals- is still unknown, but it is believed by scientists that, in the human body, viruses may outnumber the bacterial microbiome by at least 10x, making the virome out number human cells by 100 times or more. 

The human virome includes all the viruses that affect human cells, along with those that affect our bacterial, archaeal, and fungal microbiome, in addition to other viral derived genetic material.  Viruses have already been studied as important pathogens for each of these hosts, but their mutualistic and beneficial interactions are only beginning to be explored.  This is similar to the story of bacteria, which are only now being recognized for their importance in humans.  In addition, it appears there are many important, complex interactions within the microbiome that include the virome.  For example, it is likely that viruses that attack bacteria are embedded in the gut mucous and attack and destroy bacteria before the bacteria can reach the gut lining, providing host immunity.

Investigation into the viral microbiome is still at its beginning. Discovery of new viruses and their interactions with humans is likely to continue and perhaps increase with the increase in availability of viral genome information.  We encourage everyone to read the linked article.  The virome is a fascinating subject which we hope to explore in future blog posts.