The “Good” guys: the human-superorganism

Image Credit: Jon Berkeley / SPL @TheEconomist
Image Credit: Jon Berkeley / SPL @TheEconomist

“When one tugs at a single thing in nature, one finds it attached to the rest of the world.” – John Muir

Post Highlights:

  • We have over 10 times more microbial cells (estimated 100 trillion) than human cells in our bodies
  • Microorganisms make up about 1 to 3 percent of the body’s mass (in a 200-pound adult, that’s two to six pounds of bacteria) and are viewed by some scientists as an additional organ
  • Metagenomic sequencing is currently used by the Human Microbiome Project (HMP) to identify 10,000 microbial species that occupy the human ecosystem – between 81 and 99 percent of all microorganismal genera in healthy adults
  • 99% of all bacteria in the human body are either mutualists (we provide food and shelter and they help us function more efficiently) or harmless; less than 1% are disease causing in a healthy adult
  • This bacterial genomic contribution is critical for human survival – our microbiomes have been increasingly linked to disease of nutrition, heart disease, diabetes, multiple sclerosis and many other disorders
  • Our microbiomes are specialized but not monotonous: originally passed to us from our mothers, habituate to mirror those sharing the same living space, and may have plasticity of cultivation so to meet our health needs
  • Bacterial transfusions are being strategically employed to save lives of patients suffering from the vicious gut infection of antibiotic-resistent Clostridium difficile, which kills 14,000 people annually in the U.S. 

Cohabitation and the Rest of the Story

Bacteria: a word that often generates feelings of fear when mentioned in conversation.  Considering that many times our attention is drawn to the existence of bacteria in wake of sensationalized news reports of “outbreaks”.  This adverse reaction is justified rightly so.  The information that we get from the media is necessary, and many times we are alerted to events that are of accute importance to acknowledge.  However, the fear-based reaction that these news stories create are most likely due to a general misunderstanding of the symbiotic relationship that we share with our microscopic friends.

The rest of the story: Many scientists are now referring to the human body as a “super-organism” or an organism made up many organisms.  Our bodies are a thriving ecosystem for trillions of bacteria living in and on the organ systems.  It turns out that we are only 10 percent human: for every human cell that is intrinsic to our body, there are about 10 resident microbes — including commensals (generally harmless freeloaders) and mutualists (favor traders) and, in only a tiny number of cases, pathogens (disease causing). (See: New York Times article)

Colonization and Co-dependence

Some folks believe that we are the sole inhabiters of our bodies, and that the only genetic materials passed from parent to child are of human origin.  However, significant evidence paints an alternative picture of shared dependence and co-evolution between bacteria and us. http://elifesciences.org/content/2/e00458.short

Babies enter into the world from a sterile germ-free environment but the moment that a newborn passes through the birth canal, the mother’s endogenous bacteria begins to colonize.  Studies have found that a baby’s system is  immediately colonized by bacteria from the birth canal or mother’s skin when delivered by C-section.  Our bodies are continually colonized each day for the rest of our lives.  By studying fecal samples scientists have determined that we share similar microbiomes with cohabitating family members and pets (Song, SJ, 2013).

How might colonization suggest co-evolution?  For many years doctors were baffled by some of the complex carbs that make up human breast milk.  Evolutionary theory argues that every component of mother’s milk should have some value to the developing baby or natural selection would have long ago discarded it as a waste of the mother’s precious resources.  However, the human genome does not contain the enzyme coding gene to break down the complex carb oligosaccharides.

It turns out the oligosaccharides are there to nourish not the baby but one particular gut bacterium called Bifidobacterium infantis, which is uniquely well-suited to break down and make use of the specific oligosaccharides present in mother’s milk. When all goes well, the bifidobacteria proliferate and dominate, helping to keep the infant healthy by crowding out less savory microbial characters before they can become established and, perhaps most important, by nurturing the integrity of the epithelium — the lining of the intestines, which plays a critical role in protecting us from infection and inflammation. (See: New York Times article)  

…..Our gut microbes might actually be driving our appetites as well.  So when we begin to crave certain foods, it could very well be the intelligence of our bodies signaling to us that we need to increase a certain nutritional supplement to maintain healthy homeostasis.  However, we must keep in mind that many times that we have hunger pain it is actually a sign of dehydration.  Drink more water.

In previous years, it was believed that our genentic code was the key to unlock understanding of our health and potentials for disease state.  However, as we become more aware of the living ecosystems inside our bodies we are now realizing that our over-all health is also greatly attributed to the healthy baseline of the bacteria, which our longevity is dependent on.

Understanding the human genome and metagenome

The human genome is the complete set of genetic information for humans, our DNA is made up of coding and non-coding sequences.  The coding sequences are called genes and they are used to “write” the codes for a protein, which then is transformed through biochemical processes (something a little like magic, into what becomes eye color, hair, immune system, enzymes, blood types, etc.  The human genome contains about 98% genetic information that is either not transcribed into a protein or the function is unknown.  Whereas, the bacterial genome contains only 2% noncoding sequences.  The amount of non-coding DNA correlates with organism complexity and genome size; however, there are even exceptions to this rule.

Advances in DNA sequencing technologies have created a new field of research, called metagenomics, allowing comprehensive examination of microbial communities without the need for cultivation.  This technology allows a process that previously took 7-10 days to take one day.  The technology cost and speed has increased at a rate that leaves even Moore’s Law in the dust.  This is good news for us since it means that we will be able to have our entire human genome sequenced as easily as going in for a flu shot.

New biotechnology innovation from Illumina (HiSeq 2000 sequencing machine) has assisted in the metagenomic sequencing and characterization of 3.3 million microbial genes in the human gut alone.  Researchers estimate that the human microbiome contributes some 8 million unique protein-coding genes or 360 times more bacterial genes than human genes. (See: NIH NewsScientists estimate that the entire human genome, for example, has about 20,000 to 25,000 protein-coding genes (See: Scientific Journal in Nature).  

The 11T bacteria living inside us.  Check out the phylogenetic analysis below to see the family tree of our bacterial friends.

The NIH Human Microbiome Project is one of several international efforts designed to take advantage of large scale, high through multi ‘omics analyses to study the microbiome in human health. (See the infographic below for Metagenomic Phylogenetic Analysis)

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=1&_r=2&src=dayp&
Application of the Human Microbiome Project results obtained applying MetaPhlAn on the 690 shotgun sequencing samples.
Infographic credit: The Huttenhower Lab, Dept. of Biostatistics, Harvard School of Public Health

http://huttenhower.sph.harvard.edu/metaphlan

http://www.nytimes.com/2012/06/19/science/studies-of-human-microbiome-yield-new-insights.html?pagewanted=1&_r=1&src=dayp

There isn’t enough antibacterial soap or antibiotics in the world to completely rid our bodies of bacteria.  Even if there were, extricating bacteria from our systems would result in mass disfunction.

“We have defined the boundaries of normal microbial variation in humans,” said James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning and Strategic Initiatives, which includes the NIH Common Fund. “We now have a very good idea of what is normal for a healthy Western population and are beginning to learn how changes in the microbiome correlate with physiology and disease.”

 http://www.nature.com/articles/nature11550.epdf?referrer_access_token=l8hnHi25ZP2arbQ0nk79v9RgN0jAjWel9jnR3ZoTv0OVY5A-Al4l1ELdcH1RKF_2XB98h_40szxSCdizKPAM0ZZMIEKqqXMBelY9HXo5zIklGdeNC4OMY1SgBXpuUjEo

American Gut Project: http://humanfoodproject.com/americangut/

(http://www.nytimes.com/2010/07/13/science/13micro.html?_r=0)

References:
Pray, L. (2008) Eukaryotic genome complexity. Nature Education 1(1):96
Robinson, C. J. et al. (2010) From Structure to Function: the Ecology of Host Associated Microbial Communities
Sleator, Roy D. (2010) The human superorganism – Of microbes and men.  Medical Hypotheses, Vol 74 , Issue 2 , 214 – 215