Strange, parasitic microbiome bacteria may responsible for inflammatory diseases

Electron micrograph of a type of Actinomyces, the genus of the natural host of TM7, discussed in the paper.

There are many bugs in the microbiome that cannot be cultivated, and thus are incredibly difficult to study using normal culturing techniques.  We only know about these bugs through DNA sequencing, and it often difficult to draw any substantial conclusions from this information.  One such group of bugs that is highly abundant in the microbiome is the bacterial phylum TM7.  TM7 has been associated with numerous inflammatory diseases, like vaginosis, inflammatory bowel diseases and periodontitis, and DNA analysis shows that this bug has the ability to create many toxins.  Studying this bug could lead to breakthroughs in microbiome diseases, but until now it was unculturable.  Recently though, a team of scientists from around the United States were able to cultivate these bacteria and in doing so learned what makes this bacteria so unique, and possibly so pathogenic.  The results were published in PNAS.

The team aimed their investigation at the oral microbiome, because TM7 is abundant in the mouth and highly associated with periodontitis.  They took samples of spit and realized that TM7 only could grow when another bacteria, Actinomyces odontolyticus, was present.  When they cultured these bacteria together in a saliva-like media they realized that the TM7 was physically attached to the surface of A. odontolyticus.  Through further experimentation they learned that TM7 could never grow on its own, and needed A. odontolyticus to replicate.  Furthermore, TM7 is parasitic, and kills A. odontolyticus when they are starved.

The researchers then investigated the pathogenicity of TM7.  They learned that TM7 can evade detection by the immune system for itself and A. odontolyticus.  They also discovered that the particular strain of TM7 they were studying was antibiotic resistant.  Furthermore, sequencing of the TM7 showed the strain had amongst the smallest genomes ever discovered, and relies on the A. odontolyticus for production of many essential molecules, like amino acids.  However, TM7’s small genome is very dense in the production of virulent molecules and toxins, perhaps necessary for its parasitic nature, which could also affect its human host.

This study raises many interesting points about pathogens in the microbiome.  DNA sequencing is a great start to defining the microbiome, but often times culture, or in this case co-culture is necessary to drill down into the true virulence of bacteria.  For instance, prior to this study A. odontolyticus was considered to be associated with many inflammatory diseases, but these researchers showed that it is likely TM7, not A. odontolyticus that is the true culprit.  Alas, the complexity of the microbiome often times reveals many more questions than answers.

How an antibiotic resistant bacteria is raising concerns for the 2016 Summer Olympics

About a month ago we wrote about an antibiotic resistant bacteria called MRSA, or methicillin-resistant Staphylolococcus aureus, and gave an example of an athlete who had contracted the bacteria.  There is now another antibiotic resistant bacteria making international headlines and it is once again a relationship with sports that is bringing it to the forefront of our attention.  Recent reports out of Rio De Janeiro, Brazil show that an antibiotic resistant “superbug” has been found in the Cariorca River that runs through Rio and empties into the Atlantic Ocean at the famous Flamengo Beach.

This report from scientists at the Instituto Oswaldo Cruz is particularly concerning as the bacteria have been found close to the Marina da Gloria, site of the 2016 Olympic sailing competitions. This bacterium is of the Enterobacteriaceae family and produces an enzyme called KPC that is resistant to most forms of antibiotics.  This bacterium is usually only found in hospitals, so how is that it was found in three separate sites of the Cariorca River?

Well, its not yet clear how the bacteria made its way to the river, but the scientists did note that the bacteria were not found before the river made it’s way through town. This leads to the belief that it was likely sewage and waste from hospitals that transmitted the bacteria into the environment. There are several hospitals along the river and fecal matter in the sewage very well could have been host to the bacteria. Officials in Rio had stated their goal was to reduce the sewage and waste by 80% but officials have recently acknowledged that this number was not going to be reached in preparation of the 2016 Olympic games.

Like other bacteria, it is possible that someone who comes in contact with the bacteria may not get sick from it but they could carry it and pass it on to someone else. Those who do contract this bacterium will need to be hospitalized and studies have shown that KPC producing bacteria result in a 50% mortality rate. Antibiotic resistant bacteria are a major concern in today’s society and something that we feel does not get enough attention.  A recent report out of the UK that was commissioned by Prime Minister David Cameron and supported by the Wellcome Trust found that antimicrobial resistance resulted in approximately 700,000 deaths a year and this number was going to increase to 10 million people a year by 2050.  This is a staggering figure and is one of the fastest rising figures in the cause of deaths around the world. 

Almost every two years there is some major health concern at the Olympics. At the 2002 winter games in Salt Lake City we saw influenza running rampant, in 2010 at the winter games in Vancouver, Canada there was a measles outbreak, and earlier this year in Sochi we had stray dogs running loose. Now, we have antibiotic resistant bacteria on the loose in Rio and it will be interesting to see how officials in Brazil get this under control in preparation for the 2016 Summer Olympics. 

This is our last post for the week. We hope everyone has a happy holiday season and we will be back with another post on Monday.  

The Blaser hypothesis: The microbiome is programmed to kill us

Editors note: I understand that the title to this blog is a bit sensationalist, but if ever a microbiome paper called for a sensationalist headline, this is the one.

Microbiome scientist Marty Blaser (and member of our scientific advisory board) and mathematician Glenn Webb published a remarkable hypothesis last week in Mbio .  The hypothesis states that the microbiome is ‘programmed’ to protect us in our youth and reproductive ages, and then kill us in our old age.

First we must consider the enormous influence the microbiome has on our health, both positive and negative, and that we have only explored the tip of the iceberg as to the true impact the microbiome has.  Then, we must remember that the microbiome has evolved with us for hundreds of millions of years, from mother to child, and that from the microbiome’s perspective, humans are just a vehicle for reproduction.   Finally, we must acknowledge that the microbiome is subject to the same evolutionary principles as any organism or community, and that the laws of nature dictate that it attempts to fundamentally organize itself so as to optimize its population.  Once we accept these three things we can investigate how the microbiome could exert its influence on humans so as to improve its population.

A mathematical analysis was performed that showed the most prospering populations of humans, and by extent our microbiomes, occur when young children survive through reproductive ages, but then die shortly after reproductive age.  Long lasting, post-reproductive humans can actually diminish the overall population because they drain certain resources.  With that in mind it is not a stretch to consider that the microbiome may be dictating this type of population structure.  That is, the microbiome prospers when it kills its host (us) shortly after reproductive age, and that it is evolutionarily ‘programmed’ to do just that.  This type of population structure occurs in other animals, and the human age structure is unique in the animal kingdom.  Humans are pre-reproductive (pre-pubescent) for a longer time than most animals, and then are post-reproductive (senescent) for a much longer time than other animals.    

The authors go on to give examples of how bacteria may be dictating the ideal age structure (protecting children and killing senescent humans).  We know of many bacteria that exist in children that are protective but then decrease in population into adulthood.  In addition there are examples of bacteria, like Helicobacter pylori, that confer protection early in life, but then the very same bacteria can become pathogenic and cause disease later in life.  Other bacteria which cause acute infections that kill their host seem only to strike older adults.  Finally, the inflammation caused by the microbiome gets worse into old age.  In fact, many of the frailties associated with old age can be traced to the microbiome. 

It is an interesting hypothesis, and one that the reader should ponder.  While it likely can’t ever be proven, this hypothesis supports the idea that it’s a bacterial world, and we are just living in it.

Could the microbiome help solve crimes?

Much of the residue on the skin that creates a finger print can be attributable to the microbiome.

We know the microbiome varies greatly between individuals, but is it unique enough, and static enough, to be traced back to an individual?  If it is, then it could theoretically be used to tie people back to the scene of a crime.  Unfortunately not everyone defecates during their crimes, and bacteria transferred from skin can degrade rapidly.  What about hair though?  Hair is commonly obtained as evidence in many crimes because it possibly contains human DNA, however the majority does not.  In these cases can the hair be analyzed for bacterial genomes, and then traced back to the perpetrator?  A team of scientists from Australia sought to answer that question in a newly published article from the journal of Investigative Genetics.

 Scalp and pubic hair was sampled from 42 individuals for the study.  The findings showed that while each of the people shared common bacteria, they also contained many unique bacteria.  Even with very little sampling depth, just identifying bacterial phyla, rather than genus or species, was enough to differentiate the people.  This was especially true with pubic hairs, which were much more individualized than the scalp hair.  In addition, the pubic hairs very clearly differentiated males and females based on the abundance of Lactobacillus, which are very abundant in female pubic hairs (as well as the vagina).  Finally, the results showed that the hairs, especially pubic hairs, were stable over a 5 month span.

Overall this study serves as proof of concept for the microbiome being used as forensic evidence.  This could especially be true for sexual assaults where there is no other physical evidence besides pubic hairs.  Interestingly, the study found differentiation between people without characterizing bacterial species or strains.  Higher resolution sequencing would almost certainly allow for higher discrimination in individuals.  So a warning for all the criminals who read this blog, you may want to consider shaving before committing any felonies.

Bacteria in the back of our nose can cause pneumonia

I can tell you from first hand experience, getting pneumonia is not a fun experience. It can actually be quite deadly and results in approximately 1.3 million childhood deaths each year worldwide.  One of the causes of pneumonia is invasive pneumococcal disease, or a fancy way of saying a bacterial infection caused by a specific bacterium, Streptococcus pneumonia (or the pneumococcus). This bacterium often resides in the place where your mouth and nose connect called the nasopharynx. A better understanding of the relationship between this bacteria and the nasal microbiome will allow for a better ability to modulate the bacteria and prevent or treat diseases like pneumonia or meningitis.

Scientists recently published a study in the journal Microbiome that compared the nasopharyngeal microbiome of individuals who were natural carriers of this bacterium and those who were not.  In a study of 40 individuals, 10 were natural carriers of the pneumococcus and 30 were not. Those who were not were inoculated (vaccinated) through their nose with one of two strains of the bacteria.

They found that the natural carriers had greater phylogenetic distances (PD) between the bacteria in their nasopharyngeal microbiome. Phylogenetic distance is a measure of how common the ancestors of specific bacteria are. Those with a greater PD had bacteria that had common ancestors a longer time ago than those with a lower PD.  In individuals who were not carriers and were inoculated with the bacterial strains, those who had a more diverse microbiome resulted in pneumococcal carriage being established, meaning the presence of S. pneumonia, was identified in the nasopharynx.

This study provided a model for studying the interaction between the microbiome of our nose and specific bacteria that are important for disease onset. We often see that in an environment like the gut with a more diverse microbiome, bacteria are unable to colonize and establish a presence, but the opposite is true in this case. Those with a more diverse microbiome often had pneumococcus in their nose after inoculation.  It is proposed that carriage of pneumococcus results in an immunizing event and therefore the ability for the bacteria to become established is beneficial and helps establish better immunity.  Better understanding of this relationship will be important for better immunizations and preventing invasive pneumococcal disease. 

What microbes are in the food we eat?

There is a common saying “You are what you eat.” But is this actually true? A lot of attention has been paid to the microbes in our gut and the effects they have on disease and nutrition, but little has been reported on what microbes are in the food that we eat on a daily basis and the impact that this has on our microbiome and the microbial communities in our body.  A team of three scientists at the University of California, Davis set out to characterize the microbes that are in three different dietary patterns.

Published in the journal PeerJ, the scientists described the microbial communities in a typical American diet, a USDA recommended diet, and a vegan diet. The American diet consisted of convenience foods like Starbucks, McDonalds, and Stouffer’s frozen food. The USDA recommended diet consisted of foods such as fruits and vegetables, lean meat, dairy, and whole grains. The vegan diet excluded all animal products (at the bottom I have included what exactly was in each diet). 

The USDA diet contained by far the most microbes at approximately 1.3 billion per day, while the vegan diet came in second with about 6 million microbes, and the American diet last at 1.4 million microbes. The USDA diet consisted of many live active cultures such as yogurt and cottage cheese which was most likely the reason for the higher number of microbes.  

This study did not answer the important question of what happens when we ingest these foods and what impact does diet have on our microbiome.  But it opens up the door to many further questions about the impact that our diet has on our microbiome. This study was only a small study and while previous studies have shown that microbial shifts have been seen after a large change in diet, we still do not know how readily the microbes in our food colonize in our gut. While this study suggests that different diets vary in terms of the number and composition of microbes we consume, further studies need to be conducted to better understand its impact as well as other factors such as cooking techniques and processing have on our microbiome. 

As a side note, one of the authors of this study, Dr. Jonathan Eisen, writes a very interesting blog himself and if you are interested in the microbiome, I recommend you take a look. Here is his post about this recently published work.

And if you are interested in exactly what was in diets that they studied, here it is:

The American diet consisted of a “large Starbucks Mocha Frapuccino for breakfast, a McDonald’s Big Mac, French fries, and Coca Cola for lunch, Stouffer’s lasagna for dinner, and Oreo cookies for a snack.”   

The USDA recommended diet consisted of “cereal with milk and raspberries for breakfast, an apple and yogurt for a morning snack, a turkey sandwich on whole wheat bread with salad (including a hard-boiled egg, grapes, parmesan cheese, and Ceasar dressing) for lunch, carrots, cottage cheese and chocolate chips for an afternoon snack, and chicken, asparagus, peas and spinach on quinoa for dinner.”

And the vegan diet consisted of “oatmeal with banana, peanut butter, and almond milk for breakfast, a protein shake (including vegetable-based protein powder, soy milk, banana and blueberries) for a morning snack, a vegetable and tofu soup (including soba noodles, spinach, carrots, celery and onions in vegetable broth) for lunch, an apple and almonds with tea for an afternoon snack, a Portobello mushroom burger (including Portobello mushroom, avocado, tomato, lettuce, and a whole wheat bun) with steamed broccoli for dinner, and popcorn, hazelnuts and fig bars for an evening snack.”