The Human Micro Biome

There is a growing recognition that we as a species, humans that is, are not a single organism but a community of organisms living in synchrony. As scientists have recognized for many years, the human gut, skin, and digestive tract are colonized by trillions of bacteria, fungi and other microbes. What we did not realize until recently, was how important these organisms are to our health and well-being

The microenvironment of the human gastrointestinal tract reflects the interplay between bacteria, our diet, intestinal digestive enzymes, lipids, polysaccharides, amino acids, and the by-products of metabolism. The specific make-up of each individual reflects their environment, diet, and family heritage. Indeed, our bacterial flora are transmitted to us by our mothers, who prior to the advent of pasteurized baby-foods, pre-chewed their infant’s food.

More to the point, we now realize that bacterial infections and exposures to foreign antigens early in life protect and prepare us for a healthy adult life. Many modern maladies, such as asthma, diabetes, hypertension, even possibly autism and schizophrenia, may reflect infections, immune responses and the timing thereof. It has been suggested that infections with parasites modulate our immune response. In our increasingly clean environment, devoid of hookworms, tapeworms, and the like, our overactive immune system creates autoimmunity in the form of rheumatoid arthritis, systemic lupus and other maladies.

This reflects the growing recognition that human biology is in fact human ecology. The importance of this cannot be overstated when we examine human tumor biology. We are continually bombarded by the teachings of a cadre of scientists who believe whole heartedly that they can answer the puzzle of human cancer by examining the intricacies of individual human cancer cells, primarily at the level of DNA.  Nothing could be further from the truth.

Take for example just one of the myriad of signaling pathways. Beta catenin is among the most potent tumor promoters. The deranged function of beta-catenin has been identified in several human tumors including prostate, lung and colon. Its closest association being that with colon cancer, wherein the loss of the APC protein (adenomatous polyposis coli), results in a particularly aggressive form of the disease.  The APC protein normally combines with axin and glycogen synthase kinase 3 beta (GSK3B) which all together function to regulate beta-catenin. It is the loss of APC that releases Beta-catenin and drives polyps to become cancerous.

However, upstream of this triumvirate of regulatory proteins are the integrin-ca cadherin proteins that communicate across the cell membrane. By changing the environment of the colon itself, we can influence the integrins, which regulate the cadherins. This in turn regulates beta catenin.  Thus, colon cancer may not arise from changes in our genetic makeup but instead may be driven by micro-environmental changes in the colonic milieu that alter cellular behavior and drive malignant transformation.

Again and again, we are forced to recognize the complexity of human biology. Now we realize that it is not just the genome to the transcriptome to the proteome, but indeed the micro biome.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

One Response to The Human Micro Biome

  1. Mark says:

    Dear dr. Nagourney,

    Does this implicate that Dr. Simoncini was a litlle right when he told that cancer is a result of candida and fungus?
    He is talking about baking soda as a treatment, but it has never been proven if I see the medical research reports.
    Do you maybe know if baking Soda can be beneficial?
    I also red that the PH level of your body is involved with development of cancer.
    A low ph is the ideal environment for cancer I,was told.
    Do you maybe know if things like this are tru; a commen doctor tells you that it is all bull shit.
    I was even told that there is no evidence of the relation of food and developing cancer althoug I read a lot about red meat and animal protein.

    ( Holland)

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