Year: 2009

Dear Friends,

Can you name this Beautiful Creature?

Today, I will be taking you with me on a journey into the inner workings of the world of the Human Microbiome Project. When one dives into any new content area there is the requisite language/vocabulary to master. Over the last three weeks, as we have begun this journey into the HMP, we have touched upon The Roadmap, The Jumpstart Centers, The Reference Genome, Repository Sites, body sites, bacteria—genus, species and subspecies. In this email, we will add a few new terms such as the Collaborators, the PIs (Primary Investigators), Contigs, Nucleotides, Operons, and The Tree of Life.

I am honored to share with you a portion of my conversation with one of the HMP Collaborators and Primary Investigators—Joseph Petrosino PhD. Dr. Petrosino is an assistant professor of Molecular Virology and Microbiology within the Human Genome Sequencing Center at Baylor College of Medicine in Dallas, and he also plays an instrumental role as a Primary Investigator or Collaborator with the Human Microbiome Project. A PI or Collaborator is one who heads up a lab or a group of researchers involved in the Human Microbiome Project. Isn’t it interesting that they have chosen the label Collaborator for the leaders within the HMP.

Now let’s listen in to my interview with Dr. Joseph Petrosino

Q. Tell me about The Jumpstart Program, the four jumpstart centers, and your role in the HMP at Baylor.

A. The four jumpstart centers are Washington University in St. Louis, Baylor College of Medicine in Dallas, The Broad Institute at Harvard and MIT, and the J. Craig Venter Institute in Maryland. The Baylor College of Medicine is not to be confused with Baylor University. In 1967 they parted ways because of certain restrictions on government funding in regards to religious institutions. So BCM formed its own entity. These four centers were chosen for the jumpstart phase because each has been NIH sponsored sequencing centers in the US for many years and were responsible for achieving the completion of sequencing for the human genome and many of the sequences we have in data bases today.

The Human Microbiome Project started with what is called The Jumpstart Phase of the NIH Roadmap Project, which means that it has a high profile directive to spawn more research in this area through the many institutes at the National Institute of Health. Therefore they set aside a large bolus of money to send off to centers that are ready to hit the ground running. This phase of the project is called the jumpstart phase.

Q. What is the focus for each of these four centers?

A. All four centers focus on both components of the HMP research—the metagenomic analyses and the reference genome sequencing. My normal position at BMC is as an assistant professor in the Department of Molecular Virology and Microbiology. Within the HMP I function as one of the PIs (Primary Investigators) or Collaborators on the project. Specifically, I oversee the clinical DNA extraction lab. He co-directs with Sara Hylander PhD. I handle more the clinical body site sampling and analyses, while Dr. Hylander leads the Reference Genome sequencing. However, I have my hands in all aspects of the work. My expertise ranges from how to handle the samples to how to get more accurate information from them in terms of sequences to what does it all mean in the end.

Q How many body sites for microbial sampling are there?

A. There are 18 in women and 15 in men. For example there are 8 or 9 sites in the mouth (the saliva, tongue, hard pallet, soft pallet, the buccal mucosa, etc), four sites on the skin, three in the vagina and only one sampling method for the GI tract—multiple stool samples.

There has been much talk about using more invasive methods to get samples from specific site within the GI tract with a small group of volunteers. We were afraid that nobody would volunteer for the sampling because it would be like your worst doctors appointment ever. We wanted to make sure people actually enrolled. We have sequenced around 50 people now and are on the way to completing the 250 individuals who have enrolled.

Q. Describe the different finishing goals—Standard draft vs. High Quality draft?

A. The best way to describe [finishing goals] is when people suggest organisms that should be sequenced. There are several working groups involved in this. One of the things that they do is to take a look at the taxonomical tree of life and see how many organisms are in that genus or how many species within that genus have been sequenced and been looked at carefully. How discrete is that data—how many of the base pairs are known? [This then sets the stage for determining whether a draft or a high quality draft is called for] When we have a goal for a standard draft or a high quality draft, we are referring to the number of times or the number of passes that quality control goes over a genome. So for example, for a standard draft we will basically sequence the genome—the data comes off the machine, there is an assembly generated so the single reads are put into a longer set of what are called contigs—trying to get [the chromosome] to where you have one complete circle. For the most part, all bacteria have one circular chromosome, there are some exceptions, but in general most bacteria have one circular chromosome. If you look at the genome size (the total number of base pairs-nucleotides) and divide that by 1000 that will give you the number of genes for a bacteria. Most people assume that the average size of a gene for bacteria is around 1000 base pairs.

[A contig–from the word “contiguous”–is a series of overlapping DNA sequences used to make a physical map that reconstructs the original DNA sequence of a chromosome or a region of a chromosome. A contig can also refer to one of the DNA sequences used in making such a map.]

For the bacterial chromosome think of a railroad track in a circle. We will know some of the base pairs but won’t know all of them—there will be gaps. There will be certain levels of uncertainty at certain positions. With a Standard Draft there is a threshold of uncertainly that all the sequencing centers hold to. Anything above that limit must receive further reads so as to scrutinize these unknown bases. All bacteria will receive a Standard Draft, which will complete the circle, and many will receive what is called a High Quality Draft, which gives a more detailed accounting of each base in the chromosome.

I will close this portion of the email sharing a bit of our conversation regarding genes, proteins, pathways, evolution and probiotics. I had asked Dr. Petrosino how many of the genes in a bacteria’s 1000 gene collection produce the same protein—is there a redundancy? He seemed to confirm that primarily each gene produces a different protein, but one thing led to the next….as you will see.

A. There is a lot of protein production redundancy is some bacteria depending on the niche that an organism is living in. Sometimes if the host or surrounding bacteria are providing nutrients that the organism needs over a course of evolution certain genes won’t be needed. For example lets say you need a specific sugar metabolized and you are growing in nature you would need to have all the enzymes in that pathway, all the proteins in that pathway to be able to breakdown that sugar. Where as if you find you are in an environment with a host where you have landed in a spot in the body, over the course of evolution where the metabolite is right there then you don’t need all those genes to create the metabolite and those genes will start to eventually mutate and evolve away. Or acquire mutations that will inactivate those genes and then as time passes (many eons) it will be hard to distinguish that the genes were even there. Perhaps rearrangement will occur that will eliminate those parts of the genome entirely. Depending on where an organism lives will sort of dictate the genes that that organism has. If they have just happened to become a human symbiont then they may have more genes than they need for their new environment. Depending on the environment that a bacteria finds itself living in it has regulatory mechanisms available to itself that can switch genes on or off to enable them to adapt to that habitat- like using fermentation as a pathway for energy verses respiration in a more oxygen plentiful environment. Cytocines are proteins and so are most chemocines. Metabolic pathways are the result of a cell, whether it be a human cell or a bacterial cell producing proteins that will take a complex molecule like a protein or a sugar and clip off a small part and pass it on to the next enzyme in the pathway. Metabolic pathways are basically assembly lines with proteins being the stopping points on the assembly line.

OK, that is enough. I realize this last paragraph is a bit of a potpourri of ideas. But I wanted to posit these thoughts here for you, as they are coming from a Collaborator, whose on the bench, in the lab, doing the work of discovery for all of our benefit. Thank you Dr. Petrosino!

Sincerely yours,

Seann Bardell

Clinical Note:

To all of you, as our customers, thank you for your patience with our shipping over the last two weeks, as we have been moving our warehouse from Portland to Los Angeles. We are thrilled with our new warehouse’s capacity. Friday, last week we began shipping again—full throttle.

I want to encourage you to expand your thinking a bit when it comes to dosing with our synbiotic formulas. Have you tried mixing our different probiotics formulas? For example this morning and for the last week, I take one tablespoon of the Beta Glucan Synbiotic Formula and one teaspoon of the No. 7 Systemic Booster in a large glass of water—I like what it does, I like how my body feels with it. Try it. It even tastes quite good. With this mix I am getting a combination of our American collection of pedigreed good bugs (Beta Glucan Formula) with our Bulgarian collection (No. 7 Systemic Booster). Check what is in each of these formulas.

Another of our customers representing a large consortium of health practitioners suggests we follow a protocol of 1 teaspoon of our Original Synbiotic Formula in the morning and 1 capsule of our Supernatant Synbiotic Formula in the evening. With this regime, patients are getting both the American and Bulgarian collection with fiber and metabolites. Check this one out.

The Last Quiz Answer: Cinereous vultures, also called Eurasian black vultures, are the largest raptors in Eurasia, and boast an impressive 8- to 9-foot wing span. These vultures are considered “vulnerable to extinction” in Europe by the World Conservation Union. Current estimates put the global population at about 4-6,000 individuals. These impressive birds breed in mountainous and steppe areas from Spain to Mongolia and south to the Himalayas. They have been spotted on Mount Everest at altitudes of up to 23,000 feet. They form long-lasting pair bonds, and can live to be 38 years old.

Welcome to the Talking Glossary of Genetic Terms from the National Human Genome Research Institute.

Dear Friends,

Can you name this Beautiful Creature?

Over the last three weeks we have been begun our journey into the human microbiome using the roadmap set out for us by the HMP—the Human Microbiome Project. As we discussed last week, the first goal is the sequencing of 1000 organisms that will provide a benchmark against which further sequence data can be compared. The densest population of microbes in the human body lies in our gastrointestinal tract—the port of entry of our food and sustenance, but also the port of entry for toxins and pathogens.

We will focus initially on the GI tract microbiome looking at some of the organisms selected as part of the reference genome.

The Gastrointestinal Microbiome

Of the roughly 1000 microbes that represent the Reference Genome, approximately 307 different types of bacteria are from the GI tract—approximately. These numbers are constantly changing as newly discovered organisms are added and mischaracterized ones are deleted.

Of the 307 gut bacterial microbes there are 78 different Genus, with the rest representing different species and subspecies (strains). In other words, the 307 count contain 78 Genus and 129 species and sub species.

Notice the fact that many of the genus are unfamiliar to the commercial world: Alistipes, Bacillus, Bacteroides, Bdellovibrio, Bifidobacterium, Clostridium, Escherichia, Eubacterium, Fusobacterium, Kingella, Klebsiella, Lactobacillus, Malassezia, Methanobrewibacter, Mycoplasm, Neisseria, Oxalobacter, Pediococcus, Parvimones, Streptococcus, Veillonella and Yobenella.

In the Bacillus genus (a familiar genus but the following species of Bacillus are not) there are only 2 species now in the GI collection to be sequenced—alcalophilus and halodurans, whereas in the Bacteroides genus there are 32 different species and subspecies within the Reference Genome.

In the Bifidobacterium genus there are 12 species and subspecies (many familiar)—with species names such a B. adolescentis, B. angulatum, B. bifidum, B. breve, B. gallicum and B. longum, and subspecies (strains) like B. longum infantis CCUGS52386 and B. longum infantis ATCC 55813.

Other interesting numbers—the Bacteroides genus has 32 species and subspecies represented in the gut, Clostridium has 30, Escherichia has 4, Eubacterium has 12, Fusobacterium has 15, Klebsiella has 1 and Lactobacillus has 20.

Of the twenty Lactobacillus species, the following are some of the organisms (listed with their strain designations)—L. acidophilus ATCC 4796, L. brevis DSM 20054, L. hilgardii ATCC 8290, L. helveticus DSM 20075, L. plantarum ATCC 14917, L. paracasei ATCC 25302, L. reuteri CF48-3A and L. rhamnosis LMS 2-1.

The Lactobacillus genus has species in other sites—in fact, 39 other Lactobacillus species in the collection reside in other body microbiomes. Even though we are focusing on the gut in this email, I will list a few of them—L. casei (Airways), L. coleohominis DSM 14060 (Urogenital tract), L. crispatus CTV-05 (Urogenital tract), L. fermentum 28-3-CHN (Urogenital tract), L. jensenii 27-2-CHN (Urogenital tract), L. salivarius ATCC 11741 (Oral), L. johnsonii ATCC 33200 (Blood).

Each organism is listed in the HMP catalog under the following categories: Organism Name, Body Site, HMP Project Status, Finishing Goal, Gene Count, Sequence Center, Strain Repository. Here is a small sampling:

Bifidobacterium adolescentis L2-32—HMP Project Status-Complete; Genebank ID- AAYD000000000; Gene Count-2499; Body Site- GI Tract; Finishing Goal-High Quality Draft; Strain Repository-DSMZ; Sequencing Center- Washington University.

Bifidobacterium longum infantis CCUG52486— HMP Project Status-Complete; Genebank ID- ABOO000000000; Gene Count-2178; Body Site- GI Tract; Finishing Goal-High Quality Draft; Strain Repository-CCUG; Sequencing Center- Broad Institute.

Clostridium difficile NAP08— HMP Project Status-Draft; Gene Count-7349; Body Site- GI Tract Finishing Goal-High Quality Draft; Strain Repository-BEI HM-89; Sequencing Center-BCM-HGSC.

Lactobacillus hilgardii ATCC 8290— HMP Project Status-Complete; Genebank ID- ACGP000000000; Gene Count-2876; Body Site- GI Tract Finishing Goal-High Quality Draft; Strain Repository-ATCC 8290; Sequencing Center-BCM-HGSC.

Lactobacillus helveticus DSM 20075— HMP Project Status-Draft; Genebank ID- ACLM000000000; Gene Count-2154; Body Site- GI Tract Finishing Goal-High Quality Draft; Strain Repository-DSM 13335; Sequencing Center-BCM-HGSC.

Lactobacillus plantarum ATCC 14917— HMP Project Status-Complete; Genebank ID- ACGZ000000000; Gene Count-3314; Body Site- GI Tract Finishing Goal-High Quality Draft; Strain Repository-ATCC 14917; Sequencing Center-BCM-HGSC.

Lactobacillus reuteri CF48-3A—HMP Project Status-Complete; Genebank ID- ACHG000000000; Gene Count-2241; Body Site- GI Tract Finishing Goal-High Quality Draft; Strain Repository-BEI HM-102; Sequencing BCM-HGSC.

As you can see there are different strain repositories that the bacteria come from. There are a number of accredited microbial repositories in the world, all dedicated to the maintenance of accurate taxonomy and nomenclature, accurate sequencing and safe keeping of the microbial mother cultures in their care. The repository with the largest bacterial collection in the world is ATCC, located in Virginia. DSM -The German Collection of Microorganisms and Cell Cultures is locate in Braunschweig, Germany, and CCUG – Culture Collection University of Goteborg, in Sweden. Next to organism is the universal strain designation—the repository plus a number, representing their official scientific name down to the strain level. These repositories are the gold standard, accurately typing and properly naming each organism. That is why we can call them reference organisms. What must happen in the commercial probiotic world is to have organism typed by one of these repositories.

Notice the gene count of each of the above organisms. Most are around 2500 genes, but look at plantarum at 3300 and C. diff. at 7349. With bacteria each gene represents the ability to transcribe a one particular protein. This means that Clostridium difficile NAP08 can produce roughly three times more different kinds of proteins than the others listed here. Also realize that this isn’t even “a tip” from the tip of the iceberg of bugs in the gut. The HMP scientists are predicting that the collection of microbe in our human microbiome can produce 2 and ½ more proteins than our total human cells can. Isn’t it becoming clear how important this research is to our understandings of the workings of our human body in health and disease?

Next week we will go further into the current research regarding the sequencing of the different organisms, their protein producing abilities (their metabolic byproducts), and how these interact with our body’s pathways for good and for bad. I will be sharing with you my interviews with key researchers in the HMP.

Sincerely yours,

Seann Bardell

Clinical Note:

We really appreciate your feedback in regards to your use of the Therapeutic Foods. As you know we have put a few of your clinical pearls under the Clinical Notes Tab in our shopping cart. If you haven’t seen some of these notes, check them out—just log in, click on the Product tab, select a product and click on the bottle once and there you will find the Clinical Notes Tab.

Here is an email from John Adams MD- Sedona, AZ.

Great newsletter Sean!! Just great! Keep up the good work. And say hello to your fellow Rock Star Uber Doctor Klinghardt. I am reviewing his ART III DVDs and heard your reply to him regarding your Chromium with Beet.

BTW, I have a patient, a Psychologist who was in the Men That Stare AT Goats, the real one, who is chronically ill. He has a chronic opiate dependent pain syndrome of his bones. His cholesterol and subfractions were abnl high, as was his blood sugar. After 90 days on your chromium, his labs tests are all normal, prompting a freak out by his OPMD ( Old Paradigm MD). He is doing quite well thanks to you. Cool eh??

Best to you and your wife. john adams md sedona, az

Of course, we would only make your thoughts public with your request.

The Last Quiz Answer: The Red Deer (Cervus elaphus) is one of the largest deer species. The Red Deer inhabits most of Europe, the Caucasus Mountains region, Asia Minor and parts of western and central Asia. It also inhabits the Atlas Mountains region between Morocco and Tunisia in northwestern Africa, being the only species of deer to inhabit Africa.

Normal healthy intestinal bacteria, like Bifidobacterium and Bacteroides, influence immune responses and protect against the development of inflammatory diseases. A Sydney-based research team describe in Nature 461, 1282-1286 (29 October 2009) how the combination of good bacteria in the gut and a whole food diet with lots of fiber enhance the production of SCFAs which join with certain immune system proteins to down regulate inflammation.

Dear Friends,

Can you name this Beautiful Creature?

There is a profound movement, a shift of knowledge that is occuring all over the world. Even as the citizens of the world are experiencing the worst of illnesses, even as governments, corporations and foundations pour billions into a competitive rush for patented medications, an evolution of awareness is growing.

A wonderful phenomenon is taking place right in front of us—a critical sea change is occuring—a new (yet at the same time thousands of years old) perspective, a new way of looking at the practice of medicine, of conceptualizing our human body’s relationship to the world, in health and in disease, is emerging. The Human Microbiome Project Roadmap, that I will outline in this email, serves as an example of the new paradigm’s emergence. Interestingly enough, the public response to the swine flu vaccination, that I will end this email with, in the Green Facts Section, serves as a second example.

The Human Microbiome Project Roadmap:

The first component of the HMP Roadmap is the sequencing of 1000 microbes to serve as a reference genome (we described this in last week’s email) to facilitate the second component of the Roadmap— the phylogenetic and functional analysis of the metagenomic sequences produced from human body sites of approximately 250 individuals.

As mentioned last week, four institutions have been selected for the genomic sequencing—The Broad Institute (of MIT and Harvard), Washington University, Baylor College of Medicine-Human Genome Sequencing Center (BCM-HGSC), and the J. Craig Venter Institute. Of these, Baylor and Washington University have been selected to accomplish the metagenomic analysis of the 250 individuals.

Approximately 250 males and females (18 to 40 years of age, in good health status) from two geographic locations in the US will be selected for a core sampling. The collection of clinical specimens will be from multiple body sites to serve as sources of measurement of the core microbiomes associated with the oral cavity, skin, nasal cavity, gastrointestinal tract and vagina.

Let’s read together the form which illuminates the HMP’s worldview—the Consent Form given to prospective participants entitled, The Human Microbiome Project (HMP): Core Microbiome Sampling Protocol A.

You are invited to take part in a research study. Please read this information and feel free to ask any questions before you agree to take part.

Our bodies carry around trillions of microbes—bacteria, viruses, and other tiny living things. These microbes live in many places on and inside our bodies, such as the skin, mouth, nose, gut, and (in women) vagina. While we still don’t know how they do it, many of these microbes help keep us healthy, while others contribute to disease. Similarly, changes in our health can affect our microbes. So can things like where we live or work, our age, ancestry, health status, and diet—and probably many other things we don’t know about yet.

People and microbes both have nucleic acids (DNA and RNA), the material that contains genetic instructions. The microbes genetic material affects how they live with each other and how they act in our bodies. Our own genetic material also affects how we react to our microbes. All of the different kinds of microbes that live on us and in us, taken together, are called the human microbiome.

The document goes on to describe how, if they qualify as a healthy individual, that in the first part of the HMP they will collect samples from their different body microbiome sites in order to study the genetic material of their microbes. They will also take a blood sample to determine their own human genotype. That way the HMP will be able to study the genetic material of both their human cells and their microbes. This information will become the HMP’s core resource. Let’s continue to read:

This core resource will form the foundation for the second part of the HMP, in which new samples from different people—some who are healthy and some who have certain diseases—will be collected and studied. By comparing the microbes in these two sets of samples with the microbes in the core resource, and by doing experiments to see how the microbes interact with each and with their human hosts, researchers will begin to understand more about the complicated relationships between microbes and many diseases. Many researchers in universities, hospitals, non-profit groups, companies, and government laboratories around the world will use the resource we develop.

So how does the foregoing represent a budding paradigm shift that is occuring in the world of medicine?

The very consideration, and yes, acknowledgement, that our metabolic health is governed in part by the contingent of microbial genomes that reside on us and in us as we walk through life—our microbiome—is a paradigm shift in how we’ve perceived our body’s ultimate functioning, and opens the door not only to new therapies and journeys towards maintaining health, but also welcomes us into a new relationship with the life that resides outside our human cells.

The second part of the sea change that is washing over us has not so much to do with what we research but how we research. It represents a new spirit of openness, of gathering data and making it available for all who are interested. This is the very MO of the Human Genome Project, as they make even the individual subjects of their research aware that the data will not only be public but that this is the very means by which the project goals will be achieved—by allowing all to participate in advancing the research. Worldwide collaboration is the key word here and a key value we all need to embrace.

Sincerely yours,

Seann Bardell

Clinical Note:

In this week’s Clinical Note we will go over the three products on the left in the picture below. On the far left, by itself there is the freeze dried organic garlic and to its right are two of our patented products—Chromium with Beet and Fructo Borate Complex.

Fructo Borate Complex is the result of our collaboration with Eastern European scientists and American manufacturers. You might ask how does a synthesized calcium fructoborate qualify as a therapeutic food—good question? In the food chain boron is always found bound to carbohydrate. Whether it is in pears or prunes boron is tightly bound to a fruit sugar. Our supplemental boron is the first such boron to be available and through its Eastern European studies shows great potential as a powerful therapeutic nutrient. Click on its name to see its benefits. Also at the bottome of the bullets on benefits page is a link to a great monograph on this product, including references.

How to use and remember: Supports bone, joint and hormone health. We have seen its support in improving bone density, reducing arthritic pain and swelling, and increase steroid hormone levels in the blood—including Vitamin D levels. We have also had practitioners express its usefullness in opening up the breathing. Boron has been called the master mineral because it participates in so many governing metabolic functions.

Chromium with Beet is an organically bonded trivalent chromium with the nucleotides from brewers yeast as its ligands. The bonded chromium molecule is a very small allowing it to be water soluble and extremely bioavailable, which accounts for its effectiveness in lowering blood sugar levels. The red beet root add a healing touch to the liver, supporting phase II liver detox capacity. Take one BID.

How to use and remember: This product has been bench trialed against chromium picolinates and chromium polynicotinates and has been shown to be approximately three times more effective in lowering blood sugar levels.

Organic Freeze Dried Garlic is a wonderful broad spectrum antimicrobial against bacteria such as Salmonella, Staph, and Borrelia; against virus such as Herpes, against protozoa such as Crypto and Giardia and against yeast such as Candida. Yet it doesn’t harm lactic acid probiotic organisms.

How to use and remember: Many people suffer from co-infections that leave their bodies vulnerable to the pandemics of our time, such as Lyme Disease and Swine Flu. Additionally, it has been pointed out by infectious disease experts that individual with a high co-infection load are at greater risk of complications from receiving immunizations. Garlic reduced the co-fection load.

The Last Quiz Answer: Conservation biologists based in four countries gather for an emergency meeting in Vientiane, Lao PDR to address the peril of extinction facing one of the world’s most enigmatic mammals— the Saola. IT WAS DICOVERED TO WORLD SCIENCE ONLY IN 1992, can you believe that? Plus, it is not a little animal—about the size of a desert antelope. They have rarely been seen or photgraphed and have proved difficult to keep alive in captivity.

We have reached the tipping point, and the swine flu response clearly shows that a paradigm shift is occurring in the US citizenry, because of the fact that 50% of the population is choosing not to have the vaccination for H1N1, even in the face of the massive media campaign to do so. This clip of Joe Mercola’s interview with Barbara Loe Fisher, Founder of the National Vaccine Information Center, is a must view.

Dear Friends,

Can you name this Beautiful Creature?

The collection of human and microbial cells in our body produce a vast milieu of proteins through their collective genomes. These proteins function as 3-D structures that are either neutral, beneficial or harmful to us. As we look into their functioning in our body, how they combine to make the many necessary and beneficial pathways and structures, we will also see ways in which certain pathogenic proteins hamper, inhibit or destroy pathways and structures, causing our body to malfunction — effecting our long term survival—bringing the de-evolutionary hypothesis into reality.

Let’s look at what bugs are presently being sequenced or are targeted to be sequences by the Human Microbiome Project (HMP) as members of the selected group of microbes to be called the reference genomes. They were chosen by a broad consensus of scientists worldwide because they are thought to be the most likely residents of the microbiomes of the gastrointestinal tract, skin, nasal, oral, urogenital and airways. Here are the questions I will address in the coming emails:

1. What are the bugs that have been selected for full genomic sequencing—to be members of the Reference Genome?

2. What is the evidence of their symbiotic relationships with our human cells, tissues and systems—specifically what pathways, receptors, enzymes and structures do they help facilitate?

3. What is the evidence demonstrating that certain pathogens in our microbiome weaken our health and vitality? And how do they lead us down the proverbial de-evolutionary path?

Lets take a look at how the HMP answers these questions.

Reference Genomes of the Human Microbiome Project:

In order to facilitate the phylogenetic and functional analysis of the metagenomic sequences produced from human body sites, the HMP plans to sequence, or collect from publicly available sources, a total of 1000 reference genomes. The organisms included in this collection have all been isolated from a human body site. The information gained from the Reference Genomes will allow 16S RNA sequences and metagenomic sequence from uncharacterized microbiome organisms to be grouped phylogenetically with related organisms from the reference set providing information about the taxonomy of the unknown strains. Likewise, functional characterization of proteins in the reference organisms will aid in the functional annotation of related proteins contained in the sequence fragments derived from metagenomic samples.

I have discussed the issue of taxonomy many times with you individually, in classroom lectures, and in this newsletter. So far, the commercial probiotic industry has not gone through the universal scientific process of nomenclature, as all other biological sciences have done since the age of Aristotle. Almost all companies have named their species, and most certainly their subspecies, with propriety designations, to protect their “intellectual property”. This type of behavior thwarts of whole scientific process of discovery. We don’t know what bugs we are actually buying as consumers, since these organisms are not recognized with the universal scientific name, such as ATCC and other international repositories provide. As of this date, claims about organisms, are just that—in-house claims. The commercial industry needs to join the efforts of HMP and allow their organisms to go through the universal typing procedure—and get universal designations for their organisms. As you know, I have much passion for this field, and strongly believe that science needs to come first, before any commercial venture occurs.

The HMP has developed a detailed set of guidelines for inclusion of a strain in the reference genome group. They also welcome suggestions for inclusion of strains yet under consideration from groups outside their own.

The strain selection criteria that the Genome Centers are proposing to sequence are:

  • Phylogeny and uniqueness of the species– It is anticipated that the finishing or improvement of the genomes of species that represent novel lineages will enable broad representation of as many lineages as possible, regardless of other criteria, and will provide improved scaffolding for the metagenomic data that are being produced. These genomes will also provide valuable information to groups beyond those involved in metagenomics studies.
  • Established clinical significance– From the initial work with the sub-working groups, as well as from other sources and literature on the individual strains, we do have knowledge on relevance to health or disease states. We believe that any strain that has an established clinical significance to some health or disease condition should be included in the subset proposed to receive some level of improvement.
  • Abundance (dominance ) in a body site– Similarly, some strains have accompanying information on abundance and relative abundance in the various body sites. We believe that any strains that have established information on abundance in a body site should be included in the subset proposed to receive some level of improvement. Additional reasoning for these isolates include: (a) the more predominant organisms will contribute the largest number of shotgun read and thus should be sequenced to aid in identifying these reads; (b) the more prevalent organisms will most likely have a bigger impact on metabolic capabilities of the community and thus one would want to know their metabolic pathways. This can only be obtained by complete genome sequences or finished genomes.
  • Duplicate species but found in different body sites– For obvious reasons, duplicate species present an interesting data set that might have different metabolic capabilities dependent on which body sites they are found. For example on the strain Master List we currently have isolates of Gardnerella vaginalis that have been collected from vagina as well as skin.
  • Opportunity to explore pan-genomes– Again, isolates that have already been closed by other genome sequencing efforts outside of the HMP may be from other environmental niches, and by having additional closed isolates we can obtain more information on the associated pan-genomes. For example, we are all aware of the extra Megabase of DNA obtained when the genome of E. coli 0157 was compared to E. coli K12 as the finished reference genome.
  • Poor quality draft assembly that needs some improvement– In situations where a genome did not assemble well.
  • Other– In situations where there is some criteria other than those justifications listed above.

The Genome Sequencing Centers for the HMP are located at The Broad Institute (of MIT and Harvard, Washington University, Baylor College of Medicine- Human Genome Sequencing Center (BCM-HGSC) and J. Craig Venter Institute.

The percent breakdown of numbers of bacterial species to be sequenced and their respective ecological niches are: GI tract- 27% (count-307), Oral- 23% (count-269), Skin- 19% (count-220), Urogenital tract-18% (210), Airways- 12% (count-138), Blood-1% (count-7), Heart- 0% (count- 1) and Eye- 0% (count-1).

Next week we will zero in on some of the GI tract selected species and the specifics of their genomic ability enabling their proteomic contribution to the overall functioning of our body. Exciting isn’t it!

Sincerely yours,

Seann Bardell

Clinical Note:

In our two previous newsletters we have been looking at the two grouping of our synbiotic formulas—the American collection of bugs (in Oct. 7th email/newsletter) and their therapeutic food mix, and the last week the Bulgarian collection. All of our probiotics have gone through the toxonomy process.

As you can see in the picture below we have seven products left to discuss—let’s go over the four on the right. I classify these as our Oxidative Stress Reducing therapeutic foods—foods that clearly support the body’s Antioxidant Defense System.

On the far right we have Cruciferous Sprouts, and to their left we have wild blueberries —endogenous antioxidant support and exogenous antioxidant support respectively.

Cruciferous Sprouts Complex (powder) and the Cruciferous Sprouts Complex (capsules) have a slightly different profile of cruciferous sprouts (click on the links to see). The capsuled product was made for those individuals who don’t like the taste of cruciferous.

How to use and remember: Take one teaspoon or four capsules daily to enhance P2P production in every cell in the body. The glucosynolate family of molecules within this product trigger not just liver cells but all cells DNA to transcribe the production of the phase II enzymes (P2Ps) and therefore you are enhancing the body’s own ability to produce certain proteins that counteract inflammation, oxidation and that are crucial for detoxification. This ability we term endogenous Antioxidant Defense System support.

Wild Blueberry Daily and Wild Blueberry Extract were created to bring in the antioxidant, anti-inflammatory and neuro-regenerative power of the blueberry into our bodies to reduce oxidative stress. Clinical trails have clearly demonstrated the blueberry’s ability to enhance brain function—protecting it from oxidation. The same can be said for its protective benefits within our GI tract. The key portion of the blueberry providing these benefits are contain within its polyphenols—found within their purple pigment; and, is the reason we extracted the pigment to create the Wild Blueberry Extract. Additionally, we selected the Nova Scotia Wild Blueberry because it was rated by our USDA as the number one berry in North America for its oxygen radical absorbent capacity (ORAC).

How to use and remember: It takes us ¾ of a cup of blueberry to fill one capsule of the Daily. It’s ORAC score per capsule is 2000. It takes 1 and ¼ cup so to fill one capsule of the Wild Blueberry Extract whose ORAC score is 4000 per capsule. Use the Daily for prevention and the Extract for correction.

The Last Quiz Answer: The inner world of caves—beneath our feet are countless miles of cave passages with caves deep enough to engulf the Empire State Building. They are the least explored passes on earth and life abounds in this subterranian world. Here lives some of the strangest and least known animals on the planet. This amazing creature was filmed by the Planet Earth team. Frankly, I don’t know what it is. Perhaps some sort of blind salamander with radar like antenna. What do you think? Happy Halloween!

The amazing work in molecular biology keeps unfolding: 3-D Structure Of Human Genome: Factal Globule Architecture Packs Two Meters Of DNA Into Each Cell. This comes from the Broad Institute—one of the four sequencing centers used for the Human Microbiome Project.

Dear Friends,

Can you name this Beautiful Creature?

Happy Halloween! I know I am a bit early but I’ve got a great zoological marvel for you to enjoy in our “Can You Identify This Beautiful Creature?” segment. I think this one is an amazing ghoulish creature. What do you think? What is it? Where does it come from? A hint: it is not part of the microbiome (thank God!).

The Microbiome

Our adult bodies harbor ten times more microbial cells than human cells. Their genomes (the microbiotme) endows us with physiological capacities that we have not had to evolve on our own and thus are both a manifestation of who were are genetically and metabolically and a reflection of our state of well being.

Thank you for letting me quote again the above part of the purpose statement from the Human Microbiome Project (HMP). When you think about it, really get into it, as we will, each of us is more than just our collection of human cells. We are a community of a variety of cells; microbial and human cells, surviving together. As Bruce Birren, co-director of the Genomic Sequencing and Analysis Program at HMP says,

We’re not individuals, we’re colonies of creatures.

Another way to grasp the power of the microbiome is to fathom the fact that the 100 trillion microbes in our gut genetically contribute in excess of 100,000 proteins—encoding genes—that may provide essential traits not encoded in our own genome, yet are required for normal development, physiology, immunology and nutrition. We will continue to explore this subject next week as it is very fundamental to our understanding the concept of De-Evolution, and the disruption of the inter-connectedness of life itself.

Needless to say, the human microbiome is incredibly important. The holistic community has recognized for a long time the importance of a healthy GI tract, but this is not anymore a conversation amongst ourselves, but rather, the focus of many scientists at the National Institute of Health, working to map out the microbiome—and illuminate the naturopathic/holistic practice of medicine: take care of the gut! What makes this so exciting is that along with their status comes the necessary money, power and evolving technologies to create and implement the needed research to make possible great strides in our understanding of the microbiome relevance in our health and disease.

The Human Microbiome Project (HMP)

The HMP goals are to:

  • Determine whether individuals share a core human microbiome.
  • Understand whether changes in the human microbiome can be correlated with changes in human health.
  • Develop the new technologies to support these goals—such as bioinformatics.

In other words, the HMP mission is to generate new technologies that enable the comprehensive characterization of the human microbiota and analysis of its role in human health and disease. The areas of interest for microbiome analysis, within the human body, are the skin, the nasal cavity, the oral cavity, the gastrointestinal tract and the urogenital tract.

The first order of business is the complete sequencing of 1000 genomes to serve as reference genomes. These sequences will provide a benchmark against which further sequence data can be compared. There is a fundamental shift in the world of microbiology and that is the study of native microbial communities. Traditional microbiology has only been able to study isolated bacteria that can be cultured outside the body—focusing on the study of individual species as isolated units. However, relative to the human gut, most organisms cannot be successfully cultured outside their preferred habitat. This problem has been overcome by the advent of the analytical methods of metagenomics.

Metagenomics allows comprehensive examination of complete microbial communities harvested from their native habitat—for example, the gastrointestinal tract. Combining the sequenced genome information with the metagenomic analysis will enable us to identify the bacteria and to know the genetic capabilities. This will give us unprecedented information about the complexity of human microbiota communities.

The HIH Roadmap

The Human Microbiome Project is not a single project but an interdisciplinary effort under the NIH Roadmap of Medical Research. They state that to truly revolutionize medicine and improve human health, we need a more detailed understanding of the vast network of molecules that make up our cells and tissues, their interactions and their regulation. We must have a more precise knowledge of the combinations of molecular events leading to disease.

The Roadmap is a series of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but the agency as a whole can address to make the biggest impact possible on the progress of medical research.

NIH and the NIH Director

HIH includes 27 Institutes and Centers and is a component of the US Department of Health and Human Sciences. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases.

The office of the Director, the central office at NIH, is responsible for setting policy at NIH, which includes the 27 Institutes and Centers. This involves planning, managing and coordinating the programs and activities of all NIH components. Here is perhaps the most exciting part—the new Director of NIH Francis S. Collins MD/PhD.

Dr. Collins is the former head of the Human Genome Project, and is now responsible for setting a tone and policy of collaboration of research findings with scientists all over the world. There is much that I can say about this great man, but suffice it to say that it is very fortunate for all of us that he is the leader of this project. His book The Language of God (2006) is highly recommended!

So now we know a bit about the structure next week we will dive into the organisms to be researched.

Sincerely yours,

Seann Bardell

Clinical Note:

There are many wonderful organisms that work within our microbiome to help us maintain health. Last week we focused on understanding the features and benefits of the American collection of pedigreed lactic acid bacteria we use in the four synbiotic formulas pictured on the right—see the discussion in the October 14th Newsletter on our website. This week we will focus on the three on the left—the Bulgarian collection of pedigreed lactic acid bacteria.

The Supernatant Synbiotic Formula as the name implies contains good bacteria (Bulgarian bacteria) and fiber (organic inulin—a soluble fiber from chicory root). Good bugs and fiber (food for the good bugs) is defined as a synbiotic product. The Supernatant part of the name refers to the freeze dried metabolites—the enzymes, peptides, lactic acid, bacterocins, biosurfactants—the metabolic byproducts produced by these good bugs. The supernatant is isolated and freeze dried and included in the product.

This product contains L. acidophillus, L. bulgaricus, L. helveticus, L. casei, S. thermophilus, B. longum and B. infantis—all Bulgarian strains, inulin and supernatant. There are 15 billion cfu per capsule. 60 capsules in a bottle.

How to use and remember: Think of the name—Supernatant Synbiotic Formula- powerful metabolites ready to act immediately upon consumption, good bugs and fiber—food for the good bugs—pretty easy.

We designed this product to protect against hospital generated infections, such as C. diff and MRSA. It took our Bulgarian scientists one year of bench scientific trials to develop this product, testing different strains for their effectiveness towards inhibiting C. diff and Staph aureus growth. This product also can be used very effectively everyday as a general probiotic.

Cranberry Pomegranate Synbiotic Formula contains three pedigreed Bulgarian lactic acid organisms— L. acidophilus, L. casei and B. longum, supernatant, organic cranberry extract, pomegranate extract, d-mannose and inulin. Each capsule contains a 15 billion cfu.

How to use and remember: Besides being an excellent general everyday probiotic the Cranberry Pomegranate Formula was designed to support the healthy functioning of the urinary tract and bladder.

The No. 7 Systemic Booster– is a powerful combination of therapeutic foods to boost our bodies systemically. We included cranberry and pomegranate extracts and whole fruit, Supernatant and its metabolites, plus whole tart cherry and whole pineapple. The No. 7 Systemic Booster also contain our patented fructo borate for bone health, Vitamin D3, Folate, carnatine and carnicine for energy and cellular longevity, the nucleotides of barley sprouts for lowering blood sugar and inulin for fiber (there is no gluten in this product). Each teaspoon provide 10 billion cfu and 4 grams of fiber.

How to use and remember: As the name implies the No. 7 Systemic Booster is designed to boost many of the body’s systems—the gastrointestinal (the bugs and the supernatant), the urogenital—the cranberry and pomegranate; the osteoskeletal-the fructoborate; the cardiovascular-the pomegranate, Vitamin D and Folate; the immunological system with the defensive support of the good bugs and the supernatant. As we age, all of our body’s systems loose their vitality and optimal functioning. The older one is—the more important No. 7 becomes for regular systemic support.

The Last Quiz Answer: This is a blood pheasant. This species’ name comes from the fact that the males have vivid red coloring on the feathers of their breast, throat and forehead. They live in the mountains of Nepal, Sikkim, Tibet, northern Burma and the northwest areas of China. It is the state bird of the Indian state of Sikkim.