We have finally arrived at the door of the gastrointestinal microbiome, an area of our body that is increasingly recognized as having major ramifications towards securing our health or causing disease. Amazingly, it is an area of the body that is relatively unexplored. This may sound heretical in holistic circles, but the truth of the matter is that until recently we have not had the tools necessary to adequately explore the human gastrointestinal microbiome, its life forms and their metabolites.
In this email we will prepare for our journey into the gut by defining some terms necessary for our future email discussions, as we delve into this most densely packed of all microbial ecosystem- the human gastrointestinal microbiome.
What percent of the following words can you define?
Natural bioreactor … proteomics … phylotypes … 16S rRNA … metabolome … functional redundancy … metagenomics … bacteroidetes … firmicutes … 454 Life Science Pyro Sequencer.
How did you do?
The human gastrointestinal tract is a natural bioreactor programmed to break down food and supply us with the extracted energy and nutrients. It is composed of a 100 trillion microbial cells, mostly bacterial from the phyla Bacteroidetes (48%) and Firmicutes (51%). The remaining 1% of phylotypes within the gut are distributed amongst the phyla Proteobacteria, Verrucomicrobia, Fusobacteria, Cyanobacteria, Spirochaetes and VadinBE97. The gene power of this collection of organisms is estimated to be two fold that of our own human cells. What does that mean?
All human cells, except red blood cells, contain within their nucleus 23 pairs of chromosomes, one derived from each parent. Each chromosome contains a long coil of DNA depending on the length of the chromosome. If all the DNA in one cell’s chromosomes were unwound and joined together, it would stretch out 6 feet long.
There are four different kinds of bases- adenine (A), guanine (G), thymine (T) and cytosine(C). An A always pairs with a T, a C with a G. These bases are the building blocks, the 4-letter language that contain information to make every part of our body.
A gene is a locatable region of the genomic sequence corresponding to a unit of inheritance. It consists of a linear arrangement of bases that codes for a particular protein or set of protein molecules. Each human cell contains approximately 20,000 genes (the genome). Therefore, each cell has the genetic capacity to code for a minimum of 20,000 proteins. Proteins are the building blocks of life. They perform most of the basic biological tasks in organisms
Proteomics is the science of the study of proteins, particularly their structures and functions. Most proteins function in collaboration with other proteins, and one goal of proteomics is to identify which proteins interact. Proteins are partners in cell signaling cascades. Proteins are enzymes, and are the main components of the physiological metabolic pathways of cells. Proteins are messenger molecules, receptor molecules, transport molecules and structural molecules. Many of our hormones are proteins. Proteins form structures like tendons and hair; others perceive light, sense and flavors. Gene power is synonymous with protein producing power: genes encode for proteins. Proteins vary in size and shape. Some require 3000 bases of coding with the largest known protein coded with 2.4 million bases. That is a big protein!
If the human gut microbiome contains two times more gene power than that of our total human cells, then the microbiome has a total of 40,000 genes of protein producing ability. Our gastrointestinal tract is awash with a myriad of enzymes, messengers molecules, binding molecules, protein cascade molecules derived from both our human cells and our microbial community’s cells.
This is the arena that the National Institute of Health’s Human Microbiome Project is now putting their full attention into understanding. Traditionally, microbiology has focused on the study of individual species as isolated units, making it difficult to develop and inventory all of the microbes in an area such as the human GI tract. However new technologies have emerged which enable scientists to quantify the different organisms present in the milieu of an ecosystem. Instead of isolating and culturing each microbe, all of the DNA within the collected samples will be sequenced and analzyed through PCR technology and Metagenomic analysis.
Dr. Francis Collins, who will co-chair the Human Microbiome Project (HMP) states,
“Our goal is to discover what microbial communities exist in different parts of the human GI tract and to explore how these communities change in the presence of health or disease. We will likely identify novel genes and functional elements in microbial genomes that will reshape the way we think about and approach human biology.”
The goal of the HMP initially is to not only to quantify the complete microbial communities within the gut, but deep drafts of 100 species will be sequenced. Additionally, 15 representative commensals from various niches with the GI tract ecosystem will be selected for complete genomic sequencing; all to provide the blueprints of the cells biochemical and functional endowments.
In conclusion, the development of new technologies such as the 454 Life Science Pyro-Sequencer, PCR and Metagenomics has provided the sciences of genomics and proteomics, for the first time, the tools needed to rapidly sequence and analyze the whole interaction within the occult microbial ecosystem of the human GI tract. Illuminating the intimate functional relationships between our microbial self (the microbiome) and our human self will have profound effects on the understanding necessary to attain and protect our precious human health.
In our next conversation, we will continue to expand upon the hypothesized interactions within the microbiome and our human self and look at the actual discoveries that are being made.
Clinical Note: What is a synbiotic? A product that has a combination of prebiotic (food for the good bacteria) and probiotic (good bacteria) is defined as a synbiotic. Our Beta Glucan Synbiotic Formula provides a combination of healthy fibers (food for the good bugs) derived from oat bran beta glucan fiber, red beetroot fiber and chicory root inulin fiber, plus five strains of pedigreed lactic acid bacteria. This is the perfect formula for the Metabolic Syndrome patient.
The Last Quiz Answer: This amazing creature is the Tibetan Fox, who is widespread in the steppes and semi-deserts of the Tibetan Plateau, and is also present in Nepal north of the Himalayas.
Natural bioreactor – a bioreactor is a tank in which cells, cell extracts or enzymes carry out a biological reaction. Often refers to a fermentation vessel of micro-organisms. The gut is a natural bioreactor.
Proteomics – is the science of the study of proteins, particularly their structures and functions.
Phylotypes – is short for phylogenetic types. Phyle/phylon is Greek for tribe or race. Phylogenetics is the study of evolutionary relatedness among various organisms, discovered through molecular sequencing and morphological data.
16S rRNA – is the most conserved (least variable) gene in all cells. For this reason, genes that encode the 16S rRNA are sequenced to identify an organism’s taxonomic group (at the species level), calculate related groups and estimate rates of species divergence. Thousands of rRNA sequences are known and stored in specialized data bases.
Metabolome – is the collection of metabolites in a given region of the body. Metabolomics is a new born cousin of genomics and proteomics.
Functional redundancy – refers to different bacterial organisms containing similar suites of functional genes, that can be utilized if a particular probiotic species comes under phage attach and is wiped out. Thus maintaining the overall functionality of the GI tract ecosystem.
Metagenomics – is the science of quantifying the different organisms within an ecosystem
Bacteroidetes – a phyla of anaerobic bacteria that along with the Phlya Firmicutes numerically dominate the human gastrointestinal tract flora.
454 Life Science Pyro-Sequencer – state of art sequencing technological equipment that has been developed post the human genome complete sequencing, which enable scientist to take on the much more complicated sequencing entailed within the human microbiome.
Leading scientists with the Human Microbiome Project discuss in a streaming video how the gut flora is involved in how we regulate body weight, and may be a factor in the obesity epidemic. http://www.nature.com/nature/videoarchive/gutmicrobes/