Pathogenic microbiome bacteria change shape to adapt to nasopharyngeal environment

Microbiome bacteria are highly adapted to their surroundings.  They face constant pressure from the immune system as well as other bacteria, fungi, and even small molecules such as antibiotics.  It should come as no surprise then, that many of these bacteria have undergone major evolutionary adaptations to survive the human body.  Apparently, as discovered by French group and published in PLoS Genetics, one common strategy amongst many different bacteria is a shift from rod shaped to spherical shaped (coccoid). 

The scientists investigated the genealogy of bacteria for the family Neisseriaceae, which have species with a high diversity of shapes, including some members from the human nasal microbiome, like Neisseria meningitidis that are spherical.  In tracing the histories of this bug they noted that many other bacterial species showed a similar tendency, that is they converted from rod to coccoid after entering the nose.  The researchers were even able to track down the simple genetic mutations responsible, and they noted that this mutation to coccoid conferred many fitness advantages over the rod shape.  For example, the coccus shape has a higher surface to volume ratio than the rod, so that the host immune system has less surface to detect, without sacrificing as much volume in the cell.

It is interesting to look into the evolutionary developments of microbiome bacteria, because they shed light on the shared strategies of these commensals in coexisting with their host.  These adaptations actually differentiate the commensals from the non-commensals which are potentially pathogenic, because foreign bacteria don’t stand a chance of evading our immune system, especially compared to bacteria that have evolved with us throughout the entirety of human history. 

The microbiome and its influence on evolution

The interaction between a microbiome and its host species, and the impact of this interaction on both bacterium and host organism evolution, is a fascinating subject.  Known as the hologenome theory of evolution, it has been widely understood that microbiome communities and their animal hosts undergo natural selection in concert.  In other words, human and microbiome evolutionary processes are not mutually exclusive.  In the hope of gaining a deeper understanding of this relationship, a recent study published in Nature Communications examined the exact role of the microbiome in host speciation of a vertebrate organism.  Researchers explored evolutionary divergence within two subspecies of mice and examined to what extent genetic loci played a role in regulating intestinal microbiota populations. 

Four strains of mice were used to develop a unique mouse model paradigm.  Researchers collected two naturally occurring and genetically distinct mouse populations – M.m. musculus and M.m. domesticus –that are geographically isolated in Europe (see map).  Interestingly, a small “hybrid zone” exists in which both subspecies interbreed.  Researchers examined these three distinct populations and added a fourth by artificially producing a hybrid strain between both subspecies under strict laboratory conditions.  The purpose of the laboratory-bred hybrid was to control for any confounding influence from environmental factors (it has been demonstrated that environment can influence microbiome populations and gene expression).  A subsequent analysis was performed to investigate intestinal microbiome genetic profiles for both pure species and hybrid species in addition to gene expression with potential connection to pathological indications in host species. 

Pyrosequencing techniques of a bacterial rRNA gene were used to identify genetic differences between pure species and “naturally occurring” wild-hybrid species.  Bacteria community structure varied significantly in hybrid generations, both those obtained from the hybrid zone and bred in the lab.  The most significant differences were observed in the laboratory-bred hybrid generation.  Furthermore, there was a significant decrease in bacterium species richness in both wild and lab hybrid mice.  QTL mapping, a technique used to assess underlying genetic factors, displayed a low number of microbiota genomic loci present in both hybrid strains.  This finding was thought to explain a 14.1% variation in bacterial community structure, ultimately suggesting that genetic deficiencies disrupted microbiome communities. 

QTL profiling of microbiota also indicated a high frequency of genes implicated in immune system regulation.  Laboratory hybrid generations were shown to have imbalanced T-cell subset populations at various immune sites (e.g. spleen, mesenteric lymph nodes) in combination with the aforementioned alterations in bacterium community structure.  Additionally, histological analysis of intestinal mucosa revealed significant increases in inflammatory cell infiltrates and epithelial ulcerations in both wild and lab hybrid mice as compared to both purebred wild species.  The investigators suggest a discrepancy in communication between microbiome populations and the host immune cells. 

The data from this study suggest abnormal genetic architecture and irregular immune function result in an altered intestinal microbiome due to cross-breeding between two vertebrate subspecies.  The hybrid species displayed poor fitness for survival.  As suggested by the authors, species divergence, and the consequentially genetic disruptions resulting in an altered microbiota population, is perhaps responsible for generating subspecies population isolation.  This theory offers a possible explanation or contributing factor as to why M.m. musculus and M.m. domesticus populations are geographically distinct.  Obviously, evolutionary biology is an enormously complex process with many diverse and distinct influences.  However, as this article proposes, perhaps the microbiome has had a much more profound influence on evolutionary fate than we previously realized.

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.

We've domesticated chickens and cows, how about probiotics?

Domesticated pig

Desended from wild boar

I recently came across an interesting article from Nature's Scientific Reports that discusses the ongoing domestication of bacteria by humans.  We are all well aware of domestication of animals and plants, but have we ever considered domesticating bacteria? One consequence in animals is that the domestic versions does not resemble their wild counterparts.  Striking examples are the large, white domestic ducks that are actually originally descended from the common mallard, or sheeps, which do not resemble the wild mouflon.  Another consequence is that the domesticated animals lose genetic diversity.  You may have heard stories about bananas which are at extreme risk for disease because of their monogenetic cultivation, or how many farm breeds across the world are going extinct putting the entire population of that animal at risk.  In the article researchers investigated how Lactobacillus acidophilus has changed since being used in dairy foods and probiotics.

 L. acidophilus is a unique bacteria because it can convert carbohydrates to lactic acid.  Humans then, harness the bacteria to create fermented foods like yogurt.  Because of its use in yogurt, and its general recognition as being safe by the FDA, many Lactobacillaea are used in probiotics, and we have written about the results of studies using them before.  The researchers in this study examined many different strains of L. acidophilus from all over the world and dating back to 1922 to see how the species has changed.  As it turns out, much like the domesticated plants and animals, all the strains tested had incredible genetic homology, with each strain being incredibly similar to the next.  The authors believe that this strain is very robust, and that it sits in a very advantageous place in evolutionary space, so that it is difficult for mutations to take hold.  This species can be thought of as an evolutionary bottleneck.  This may have given this strain an upper hand in being selected by early manufacturers, who did not want variation between batches and starter cultures.

 One may wonder though, does this put L. acidophilus at risk for disease?  As it turns out the bacteria appears to be very resistant to disease.  While it is attacked by many phages, these do not seem to affect the overall reliability of the species.  Again, this resiliency speaks to its use in manufacturing.  So the next time you are downing some delicious greek yogurt, remember that it likely tastes the same as when the ancient greeks were eating it too!