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From the Townsend Letter
June 2019

Postbiotic Metabolites:
The New Frontier in Microbiome Science

by Ross Pelton, RPh, PhD, CCN
Scientific Director, Essential Formulas
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The human microbiome is now known to be relevant to virtually every branch of science, medicine, and human health; and microbiome science is evolving rapidly. The purpose of this article is to summarize the history of the human microbiome and to introduce readers to postbiotic metabolites, which is the new frontier in microbiome science.
     
Louis Pasteur (1822-1895) was the first microbiome scientist. Pasteur made breakthrough discoveries regarding vaccination, microbial fermentation, and pasteurization. Pasteur's medical discoveries enabled him to create cures for many of the world's major killer diseases during his time including rabies, anthrax, tuberculosis, cholera, and smallpox. Consequently, Pasteur became known, respected, and loved throughout the world; and he was the first scientist to become an internationally known "global rock star."

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Pasteur's accomplishments are absolutely mind-boggling. A modern-day equivalent would be if one scientist today single-handedly created cures for cancer, heart disease, diabetes, and Alzheimer's disease. However, Pasteur's accomplishments also ushered in the widespread belief that germs are the cause of diseases, which initiated the germ theory of disease.1 This resulted in a century of bacteria-phobia and gave rise to the era of antibiotic drugs. However, during the past several decades, the over-prescribing of antibiotics has resulted in microbiome destruction, weakened immune systems, and the rise of deadly antibiotic-resistant "superbug" infectious diseases.
     
Elie Metchnikoff (1845-1916) was a Russian-born scientist who developed an interest in the study of beneficial microbes. In 1888, Metchnikoff traveled to Paris to meet Pasteur and ask Pasteur's advice regarding some difficulties he was experiencing with his research. Pasteur was impressed with Metchnikoff and invited him to stay, setting him up with his personal laboratory. In 1904, Metchnikoff was promoted to deputy director of the Pasteur Institute where he remained for the rest of his highly productive career. In 1908, Metchnikoff won the Nobel Prize for medicine for his discovery of phagocytosis and its importance to the immune system.2
     
At the Pasteur Institute in the early 1900s, Metchnikoff became increasingly interested in human health and longevity. He learned that Bulgaria had a disproportionately high number of healthy elderly citizens. He conducted a study and compiled statistics from 36 countries, which led him to discover that Bulgaria had more people who lived to be 100 years of age than any of the other 36 countries he surveyed.
     
Researched NutritionalsMetchnikoff believed that the aging process resulted from the activity of "bad" bacteria that produce toxic substances in the intestinal tract. According to Metchnikoff, these toxic compounds were responsible for what he referred to as "intestinal auto-intoxication," which caused the physical deterioration and breakdown associated with aging.
     
And then, Metchnikoff had a tremendous intuitive insight that made him the "Founding Father of Probiotics." Metchnikoff believed that the long healthy lifespans of Bulgarians was related to their daily consumption of fermented milk products like yogurt and kefir. He knew the bacteria responsible for the fermentation of milk produced lactic acid, which created an acidic environment in the GI tract. He theorized that the lactic acid created a slightly acidic environment, which, suppressed the growth of toxin-producing bacteria. The net result was a reduction of "intestinal auto-intoxication," which resulted in better health and longer life.
     
In 1907, just two years after making his landmark proposal that the ingestion of Lactobacillus bulgaricus was responsible for the health and longevity of Bulgarians, Metchnikoff published his findings in his book titled, The Prolongation of Life: Optimistic Studies.3 Consequently, Metchnikoff is also credited as the founding father of the life extension movement.

The Modern Era of Microbiome Science
The human microbiome refers to the organisms (bacteria, fungi, and viruses) that reside in and on our body. When I use the term microbiome in this article, I am limiting its scope to the bacteria that reside in the gastrointestinal tract.
     
The Human Genome Project, which cost an estimated $3 billion, was a 13-year (1990-2003) project that resulted in the first successful sequencing of the human genome. Scientists hoped that sequencing the human genome would lead to cures for many of today's chronic degenerative diseases. That goal was a complete failure; sequencing the human genome never led to successful treatments for any diseases.
     
However, one great benefit that emerged from the Human Genome Project was the development of incredible technology that allows scientists to sequence genomes rapidly and at a vastly reduced price. For example, in January 2017, Illuminia, which is the world's leading producer of next-generation sequencing technology, announced that their new NovaSeq™ could sequence a genome in one day for only $100.4 From 13 years and $3 billion to one day for $100. How's that for rapid scientific advancement!
     
The incredible power and speed of the new gene sequencing technology were partly responsible for the government's funding of the Human Microbiome Project (2007-2012).5 Subsequently, the Human Microbiome Project resulted in the publication of over 350 studies, which are viewed as the "birth" of the modern era of microbiome science. In May 2016, the Obama administration committed to continue supporting microbiome scientific research by funding the National Microbiome Initiative. This program is sponsored with $121 million in funding from federal agencies and an additional $400 million from non-government institutions.6

The Genome Complexity Conundrum
When scientists successfully sequenced the human genome, they discovered that humans have about 23,000 genes, which is substantially fewer than they expected. This finding initially caused scientists to shake their heads in disbelief and created a situation that became referred to as the "genome complexity conundrum."7
     
IMMH 2019The challenge was due to the following facts. Whereas humans have about 23,000 genes, the common rice plant (Oryza sativa) has about 45,000 genes. This led scientists to scratch their heads and say or think, "If we humans are as complex and evolved as we think we are, how can it be that we only have half as many genes as the common rice plant?"

The answer to the genome complexity conundrum began to emerge when scientists discovered that the intestinal tract of most humans is home to an estimated 100 trillion bacteria. A human harbors from 500-1,000 different species of bacteria and these bacteria contain over 3.3 million non-repeating genes. This means that over 99% of the DNA in your body is the DNA of your bacteria. This explains why humans can "get by" with only 23,000 genes. Bacteria utilize the information contained in their vast amount of DNA to produce compounds that are responsible for directing and regulating a great deal of the functioning of the human body. This explains why it is so critically important for people to learn how to create and maintain a healthy microbiome. Your bacteria are involved, either directly or indirectly, in the regulation and control of much of what happens in your body.
     
This realization has also resulted in a new understanding of what it means to be human as scientists began to realize that we are not just the product of our human genes. Instead, we are a bacteria-controlled superorganism. We are not just "us"…we are "us" plus "them."

Postbiotic Metabolites: The New Frontier in Microbiome Science
As scientists started to realize how incredibly important our probiotic bacteria are in the regulation of health, they began looking for mechanisms. How and why are probiotic bacteria capable of regulating so much of our human biological functioning?
     
Probiotic bacteria are amazingly complex little chemical manufacturing plants. Their metabolic processes enable them to digest and ferment the fibers in foods, which results in the production of a wide range of health-regulating compounds that known as "postbiotic metabolites."
     
A PubMed search reveals that "postbiotics"8,9 and "postbiotic metabolites"10 are terms that are used with increasing frequency in the title of scientific studies. In The Mind-Gut Connection, respected author and microbiome scientist Emeran Mayer, MD, states that our bacteria utilize the information in their millions of genes to transform the food people eat into "hundreds of thousands of metabolites."
     
A pronounced shift is taking place in microbiome science. Until recently, a large portion of scientific research was devoted to isolating, identifying, and naming different species of bacteria. In the new frontier of microbiome science, much more emphasis is being focused on identifying the compounds that various strains of bacteria produce, learning to understand the health-regulating effects of these compounds, and discovering which strains of bacteria are more efficient at producing these health-regulating compounds.

Balance and Diversity: Critical Factors for Microbiome Health
 Diversity refers to how many different strains of bacteria are present in the intestinal tract. Numerous human clinical trials report that a more diverse microbiome equates to better health.11,12 Scientists estimate that a healthy human microbiome contains approximately 1,000 different species of bacteria.13 On the other hand, low bacterial diversity in the intestinal tract can contribute to various diseases such as obesity14 and inflammatory bowel disease.15

The Fiber Gap: America's #1 Nutritional Deficiency
Fiber is the required food for your probiotic bacteria. A recent article titled "The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition" discusses how low fiber diets are affecting people's microbiome and ultimately, their health. The authors of this study report that an alarming 90% of children and adults in America DO NOT consume the recommended amount of daily dietary fiber.16 Scientific studies provide convincing evidence that the microbiome is the very foundation of health.17,18 It is becoming alarmingly clear that the Standard American Diet, known as the SAD diet, is more than just SAD, it is killing people.19
     
It's not enough to only take probiotics, you must learn to feed your probiotic bacteria well. Non-digestible carbohydrates and fibers are the "food" that your probiotic bacteria require. Different species of probiotic bacteria thrive on different kinds of fibers that are present in different kinds of plant-based foods. Eating a more diverse fiber-rich diet is the way to develop and maintain a more diverse microbiome. If your probiotic bacteria are not supplied with a diverse, fiber-rich diet, they will not thrive and survive.
     
The quantity of fiber in the daily diet is not the only fiber issue. A diversity of fiber-rich foods is required to promote the growth of a diverse microbiome. How many different kinds of colored, fiber-rich fruits and vegetables are you feeding your probiotic bacteria today?
     
Many people now take probiotics, which is confirmed by the dramatic increase in sales within this category. In 2005, sales of probiotics in the United States was $764 million.20 In 2014, probiotic sales reached $1.41 billion, and from 2014 to 2017, sales nearly doubled to $2.14 billion.21 However, since the vast majority of Americans are not consuming high-fiber diets, it can be assumed that many people are not getting much benefit from the probiotics they are taking.
     
For an easy way to increase the diversity of fiber-rich foods in your daily diet, I suggest you watch my 8-minute YouTube video which teaches people how to save an enormous amount of time making salads that contain a wide variety of fiber-rich vegetables. Just Google: Ross Salad Buzz.

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