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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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Balance is also a critical factor in healthy microbiome. Unfortunately many people who purchase probiotics have the mistaken understanding that more is better. It is now common to see products claiming to be superior because they contain 50 billion bacteria or even 100 billion bacteria per dose. The fact is, massive doses of just one or several strains of probiotic bacteria does not promote microbiome balance; they actually work against balance, and this is why. Probiotics that deliver very high doses of just one or several strains of bacteria can cause the immune system to trigger an alarm reaction. The authors of one study made the following statement in their conclusion, "Probiotics can be ineffective or even detrimental if not used at the optimal dosage for the appropriate purposes."22

Balance and greater diversity are imperative because these factors result in the production of a broader range of postbiotic metabolites. Some of their benefits include reduced inflammation, regulating the acid/base balance in the GI tract, directly fighting pathogens, regulating digestion, absorption of nutrients, detoxification, regulating the immune system, gut-brain communication, and much much more. Remember, in The Mind-Gut Connection, Dr. Meyer stated that your bacteria would produce "hundreds of thousands of metabolites." This is why postbiotic metabolites are now becoming the new frontier in microbiome research.

Transfer Factor Multi-ImmuneA Microbiome Analogy
The "goal" in an automobile manufacturing plant is the production of vehicles such as cars, trucks, SUVs and vans. The workforce in an automobile manufacturing plant consists of hundreds of employees with a wide variety of skills and talents. However, the skills and abilities of this workforce are largely ineffective unless they have the thousands of parts that are required to produce different kinds of vehicles.
     
Similarly, in your microbiome, you have between 500 to 1,000 species totaling an estimated 100 trillion bacteria that function as the workforce. However, your probiotic "workers" must have available a wide variety of fiber-rich foods (the parts) in order to create the desired end products, which are the postbiotic metabolites. Probiotic bacteria are primarily a "workforce," and their "job" is to build/create postbiotic metabolites.

Dysbiosis
Dysbiosis is generally considered to be an imbalance between the good and bad bacteria in the intestinal tract. However, dysbiosis is more than just bad bacteria. In dysbiosis, the gastrointestinal environment or the microbiome ecosystem has become upset and damaged. In addition to bacterial imbalance, the acid/base balance is usually far too alkaline, the cells that line the GI tract are highly inflamed, the protective mucous layer can be compromised, the gut barrier is damaged and allows intestinal permeability, and cell-to-cell communication and gut-brain communication is dysfunctional. Ideally, the best way to fix gut dysbiosis problems is to address the whole microbiome ecosystem.

MicrobiomeThe Microbiome Ecosystem's Two Pieces
Postbiotic metabolites are the compounds that control and regulate the microbiome ecosystem. There are two pieces to this puzzle. Probiotic bacteria AND fiber-rich foods are needed to produce postbiotic metabolites. And, a wide diversity of probiotic bacteria AND a wide diversity of fiber-rich foods are necessary in order to have a wide diversity of postbiotic metabolites produced.

Reestablishing the Microbiome Ecosystem
Most people take probiotics to address dysbiosis-related intestinal problems. However, for probiotics to be effective, those bacteria need access to high-fiber foods in the GI tract. Then, the bacteria have to begin the process of breaking down the foods so they can access the fibers and start the process of converting fibers into postbiotic metabolites. This process takes time.
     
Confounding the process is the fact that the ingested probiotic bacteria are likely entering into a very hostile environment that is highly inflamed, 10 to 100 times too alkaline, and overrun with "hostile" pathological bacteria. As an analogy, consider the problem of sending Eskimos to fight in the Sahara Desert, or desert nomads to fight in freezing Alaska. They will have great difficulty being effective.

The Benefits of Fermented Food
Fermentation is a process in which bacteria break down sugars, carbohydrates and fibers in foods and convert them into alcohol and organic acids. Fermentation has been used by humans for thousands of years as a method to preserve foods. Over time, people realized that fermented foods also conveyed health benefits.
     
BDNF EssentialsUntil recently, people thought the health benefits from fermented foods such as sauerkraut, kimchi, miso,and tempeh were due to the ingestion of probiotic bacteria contained in the fermented foods. However, it is becoming clear that the food preservation properties AND the health benefits from fermented foods are primarily due to the postbiotic metabolites produced by the bacteria during the fermentation process.23
     
Several metabolites produced during fermentation are classified as short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acid. These small molecular weight acidic compounds are postbiotic metabolites that play a critical role in food preservation because they create a slightly acidic pH which inhibits the growth of pathogens.
     
Recent human clinical trials have revealed strong associations between consumption of fermented foods and improved health for conditions such as obesity,24 type 2 diabetes,25 hyperlipidemia,26 hypertension,27 osteo-porosis,28 and depression.29 These studies emphasize that an individual's probiotic bacteria and the postbiotic metabolites they create have important effects far beyond just gut health.

Directly Ingesting Postbiotic Metabolites = FAST ACTION
As mentioned previously, it takes time for ingested probiotic bacteria to locate fibers, break them down and produce postbiotic metabolites. A faster and more effective way to address dysbiosis-related problems is to ingest postbiotic metabolites.
     
When ingested orally, postbiotic metabolites immediately begin asserting their health-promoting activities such as readjusting the acid/base level, reducing inflammation, accelerating the growth of healthy new cells in the lining of the GI tract, "fighting" and killing pathological bacteria, and re-establishing healthy gut-brain communication. This circumvents the time-consuming process of probiotic bacteria needing to locate fibers and begin producing postbiotic metabolites.

Metabolomics and Metagenomics
Metabolomics and metagenomics are two scientific disciplines that are barely twenty years old. These relatively new fields of science are developing very fast, in large part, due to the fundamental importance of the microbiome.
     
Metabolomics is the branch of science that identifies small molecule metabolites in biological systems, such as the postbiotic metabolites produced by bacteria in the gastrointestinal tract. Rapid advances in metabolomics have resulted in the discovery of thousands of bacteria-produced small-molecule metabolites, or postbiotics.30
     
Microbes run our world. The new science of metagenomics is unlocking the secrets of our microbial planet. Metagenomics, defined as the genomic analysis of microorganisms, is discovering the genes in bacteria that are responsible for the production of postbiotic metabolites.31
     
A couple of terms that are synonymous with postbiotic metabolites are microbial metabolites and bacterial metabolites. In a review article titled "Bioactive Microbial Metabolites," the author states that as of 2002, over 22,000 bioactive secondary metabolites are published in the scientific literature.32 And, in The Gut-Mind Connection, Dr. Mayer noted that we will ultimately learn that bacteria probably produce hundreds of thousands of metabolites.

Postbiotic Metabolites
Some of the better known postbiotic metabolites include the following:
a.   B-vitamin synthesis (biotin, cobalamin, folates, nicotinic acid, pantothenic acid, pyridoxine, riboflavin, and thiamine)33
b.  Vitamin K34
c.   Short-chain fatty acids (SCFAs): acetic, propionic and butyric acid.35
d.  Glutathione: synthesized by Lactobacillus fermentum ME3.36
e.  Antimicrobial peptides (AMPs)37
f.   Phenyllactic acid38
g.   D-amino acids39
h.  Hydrogen peroxide40
i.    Volatile organic compounds (VOCs)41
j.    Phytoestrogens: Equol, enterolactone, enterodiol.42
k.   Urolithin A and urolithin B43
l.    Fulvic acids44
     
It is beyond the scope of this article to attempt to name and list the health-regulating effects of thousands of microbial metabolites/postbiotic metabolites that been identified to date.

Dr. Ohhira's Probiotics® : Directly Delivering Postbiotic Metabolites
Dr. Ohhira's Probiotics is a fermented food product that is produced utilizing a multi-year fermentation production process under cleanroom conditions. The initial process takes place in large 80-gallon fermentation vats. Dozens of different kinds of organically grown foods (vegetables, fruits, seaweeds and mushrooms) are shredded and added to the fermentation vats along with 12 strains of probiotic bacteria. Then the bacteria are allowed to ferment/digest the high-fiber prebiotic foods they have been supplied with for a period of three to five years, which results in the production of a wide range of postbiotic metabolites.
     
There are two versions of Dr. Ohhira's Probiotics. The Original Formula undergoes three years of fermentation. The final product is a thick, dark-colored paste-like substance that is encapsulated and is sold at the retail level in fine health food and vitamin stores throughout the United States.
     
The Professional Formula originates by transferring paste from the 80-gallon vats after the initial three-year fermentation cycle into different containers for an additional two years of anaerobic fermentation. Over 99% of your microbiome consists of anaerobic bacteria that reside in your large intestines and colon. Thus, the additional two years of anaerobic fermentation results in the production of larger amounts of the postbiotic metabolites from the anaerobic bacteria. The Professional Formula is primarily marketed to healthcare professionals.
     
Dr. Ohhira's fermentation production system simulates nature. Humans ingest food into our digestive tract where bacteria convert the food into a wide range of health-regulating postbiotic metabolites. Dr. Ohhira created an external system that allows probiotic bacteria to function like they do in the GI tract, which results in the production of postbiotic metabolites.
     
Recent research conducted by an independent laboratory in Japan reported that Dr. Ohhira's Probiotics contain over 400 different postbiotic metabolites.45 This explains why Dr. Ohhira's Probiotics has achieved a reputation for rapidly improving dysbiosis-related intestinal symptoms. When taken, the postbiotic metabolites immediately begin to initiate healthy changes in the intestinal microbiome ecosystem.
     
Because postbiotic metabolites have such wide-ranging health-regulating effects, postbiotic metabolites are now being recognized as a new frontier for the pharmaceutical industry. Drug companies recognize that medications based on postbiotic metabolites will be more stable and have far fewer side effects because they are based on compounds that are naturally produced in the body.46
     
Postbiotic metabolites are now being recognized as a form of communication in the body. A recent article titled "Human Microbial Metabolites as a Source of New Drugs," in the journal
Drug Discovery Today, reviews the rapidly emerging science about how postbiotic metabolites communicate with the immune system and various organs in the body to regulate many aspects of human health.47 The mechanisms behind these health-regulating effects involve what scientists call "cross-talk" between the probiotic bacteria-produced metabolites and receptors on cells throughout the body.

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