How Postbiotic Metabolites Impact Health: Exploring New Frontiers of Probiotic Science with Ross Pelton, RPh, CCN

Sponsored by Essential Formulas Incorporated

By Natural Medicine Journal

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In this interview, Ross Pelton, RPh, CCN, describes the new science associated with postbiotic metabolites and their impact on health. Listeners will also discover what postbiotic metabolites are and why they are so important to the human microbiome.

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(Approximate listening time: 31 minutes)

About the Expert

Ross Pelton, RPh, CCN, is Essential Formula's director of science, in addition to being a practicing pharmacist, clinical nutritionist, and health educator in Southern Oregon. Pelton earned his bachelor of science in pharmacy from the University of Wisconsin. A certified clinical nutritionist, Pelton was named as one of the Top 50 Most Influential Pharmacists in the United States by American Druggist magazine for his work in natural medicine. Pelton teaches continuing education programs for healthcare professionals to use natural medicine and integrate it into their practices. He also has authored numerous books, including The Drug-Induced Nutrient Depletion Handbook, which is a gold-standard reference book for health practitioners.

About the Sponsor

Essential Formulas

Essential Formulas Incorporated (EFI) was established in 2000 as the sole US distributor of world-renowned microbiologist Dr Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products. Always an innovator, EFI introduced REG’ACTIV in 2015, containing ME-3, a probiotic catalyst that produces the “master’” oxidant glutathione inside the body's cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive, and comprehensive pro-health products for the entire family. EFI continues to flourish and grow through a strong company and product integrity and the knowledge that they’re providing scientifically proven products that positively impact the health and well-being of their customers.


Karolyn Gazella: Hello. I'm Karolyn Gazella, the publisher of the Natural Medicine Journal. Today, we have a fascinating topic. We'll be talking about postbiotic metabolites with probiotic expert Dr Ross Pelton who is also an integrative pharmacist. Before we begin, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Dr Pelton, thank you so much for joining me.

Ross Pelton, RPh, CCN: Hi, Karolyn. It's nice to be with you.

Gazella: Well the research regarding the human microbiome is really exploding. Why is this so significant?

Pelton: Well I like to give people a little historical overview which I think gives us an understanding of how and why this incredible acceleration of research into the microbiome has taken place. I'd like to go back to the Human Genome Project. It took 13 years and billions of dollars to sequence the first human genome. After sequencing the human genome, one of the primary goals of that whole scientific endeavor, they thought once they sequenced the human genome we would be able to get cures for many of our chronic degenerative diseases.

That primary goal of the Human Genome Project was a total failure. We did not get any cures for human diseases from the Human Genome Project, but one important thing that we did get was the development of incredible technology and incredible equipment that allowed for much faster and much cheaper sequencing of genomes. That's when scientists started to use this new technology to sequence the genomes of bacteria in the human gastrointestinal tract. They were astounded with what they found, this whole massive population of organisms in the human gastrointestinal tract. Fortunately, our government then went on to fund the Human Microbiome Project. The funding for the Human Microbiome Project coupled with the incredible technology developed in the Human Genome Project allowed scientists to make tremendous progress in exploring and identifying many of the different species and strains of bacteria in the human microbiome.

Now, a little historical overview. Bacteria were discovered several hundred years ago, and scientists like Louis Pasteur had a major impact on the development of microbiology and the study of bacteria. But Louis Pasteur was responsible for the gene ... Excuse me. The germ theory of disease. He solved most of the serious diseases of his time. He developed vaccines for them and taught people how to avoid them or limit their problems. He was a global rock star in his lifetime because he solved most of the common diseases of his time. It would be similar if one person today solved Alzheimer's disease and cancer and diabetes and autism or something. It's amazing what he did, but he set in motion this germ theory of disease. For a couple of centuries, most people had the concept that germs or bacteria were bad. They're causing disease and we need to eradicate them.

Well another thing that happened along the way is that the only way scientists could study bacteria was extract them from the body, put them on what's called a Petri dish on an auger plate that allows the bacteria to grow, and then they watched them and observed it. A couple hundred years, that's the only way we could study bacteria, but we've recently learned that over 99% of your bacteria are anaerobic which means they can't stand oxygen. For a couple of hundred years, scientists would extract bacteria, put it in the lab to look at it, but it would get exposed to oxygen and die. For several hundred years, we could not study over 99% of the bacteria in our microbiome, but the development of this incredible technology from the Human Genome Project allowed scientists to start to dive into this new area and sequence the genomes of the bacteria and start to learn what they are and how they function. That's what started to kind of explode the research into the human genome, the human microbiome.

Also a very interesting thing happened. There's a thing that I refer to as the genome complexity conundrum. This is a fact that, when the human genome was sequenced, we found out that humans have about 23000 genes which is significantly less than scientists thought they would find, but the conundrum is that the common rice plant has around 45000 genes. Scientists are scratching their heads. How could we as evolved beings as we are have only 23000 genes and the common rice plant has over twice as many genes as we do? The answer to this conundrum is the fact that, although we only have 23000 genes, the bacteria in our microbiome have millions of genes. In fact, over 99% of the DNA in your body is the DNA of your bacteria.

This starts to open up an understanding of how important it is to create and maintain a healthy population of these bacteria in your microbiome so that they are doing good work for you. Because if you have pathological bacteria, their DNA and their genes are creating bad compounds that cause inflammation and poison you and create all sorts of diseases. This ... We're starting to understand why it is so important to create and maintain a healthy microbiome because your bacteria in your gastrointestinal tract are controlling and regulating vast amounts of your health.

Gazella: Well I have-

Pelton: It's kind of a little overview for starters.

Gazella: Yeah. I have to say I love that historical perspective because it provides the perfect backdrop for today's conversation. Thank you. It was very thorough.

Pelton: Sure.

Gazella: Now today, I'd like to focus on postbiotic metabolites because, as you have referred to in your recent presentation, this really is a new frontier in probiotic science. Remind us. What are postbiotic metabolites?

Pelton: This is another fascinating area, Karolyn. It's just starting to be explored, but it's extremely important when it comes to microbiome science. [inaudible 00:06:39] say in my lectures and seminars the reason probiotic bacteria is important is because of the work they do. The work that they do is that their metabolic processes digest the food that you give them and break it down and, in turn, their metabolic processes produce a wide range of compounds that we're referring to as postbiotic metabolites. What's really important for people to understand is it's these compounds that the bacteria produce that regulate vast amounts of your health, not the bacteria themselves.

We're shifting our focus a little bit from putting all our research efforts and all of our money into just identifying and naming different strains of bacteria. Now, we're starting to realize it's probably more important to identify what are the compounds that these bacteria produce, what are the health regulatory effects of these compounds, which strains of bacteria are more efficient and more effective at producing some of these compounds. That's the new frontier in microbiome science. Two months ago, I gave a presentation at the International Probiotic Association's annual convention in Miami. The title of my presentation was Postbiotic Metabolites: The New Frontier in Microbiome Science. This is what we're starting to explore and understand now.

Gazella: Yeah. It sees like it's taking this science ... It's giving it a whole new level of complexity. Let's talk a little bit about practical things like what functions do these metabolites serve as it relates to the human microbiome and health in general.

Pelton: Sure. That's a good segue here. I'm emphasizing these postbiotic metabolites. What do they do? Well they have a vast number of functions, and in fact, a very highly respected author and scientist in the microbiome arena—his name is Dr Emeran Mayer—wrote a book called The Mind-Gut Connection. In his book, he tells us that your bacteria with their millions of genes will digest your food and produce hundreds of thousands of metabolites. We're just beginning to understand what all these metabolites, these postbiotic metabolites are. Some of their functions, they have antiinflammatory activity. They adjust the acid-base balance in the GI tract. They have cell signaling capabilities. They have detoxification capabilities. They can directly fight and kill pathological bacteria. There's just a wide range of functions.

Let me just mention one major class of these postbiotic metabolites. They're called short-chain fatty acids. This is a class of really important postbiotic metabolites produced by your probiotic bacteria. Since they're acids, short-chain fatty acids, they're weak acids, but they create the proper and optimal acid-base balance in the gastrointestinal tract. The optimal acid-base balance is just slightly acidic, but when people have dysbiosis ... That's the term for different types of gastrointestinal problems or you have gas or bloating or diarrhea or constipation or inflammation or pain or whatever. Dysbiosis is the term for these general conditions. When people have dysbiosis or gastrointestinal problems, the acid-base balance goes anywhere from 10 to 100 times too alkaline. If you're going to get the GI tract back to good health, you have to bring it from it's alkalinity back down to its slightly acidic condition, and these short-chain fatty acids produced by the probiotic bacteria readjust and create that optimal slightly acidic acid-base balance.

Short-chain fatty acids also have antiinflammatory activity. If you have dysbiosis and gut problems, you've got inflammation. They'll help to dampen that inflammatory fire. Also another really important part of this in the story with the short-chain fatty acids is the fact that the cells that line your gastrointestinal tract have the most rapid rate of turnover of any cell in the human body. People don't realize this. Most people don't, but you create a whole new digestive tract every 6 to 10 days. It takes an enormous amount of energy for the body to continually generate these new cells in the lining of the gastrointestinal tract, and you do not get the energy to produce these new cells from your blood supply. The energy comes from short-chain fatty acids like butyric acid that are produced by your probiotic bacteria, these postbiotic metabolites.

These are just some of the ways one class of postbiotic metabolites, the short-chain fatty acids, contribute to a wide range of health-related things related to your gastrointestinal tract.

Gazella: Now, can you expand a little bit more on the mechanisms of action and how these metabolites kind of work on our behalf? I mean the short-chain fatty acids is a great example.

Pelton: Sure. Again, there's a wide range of these different compounds, and so there's different mechanisms depending on what postbiotic metabolite the particular strain of bacteria are producing. This gives me a chance to emphasize a really important point, Karolyn. A healthy microbiome is a widely diverse microbiome. By diversity, I mean a lot of different types of probiotic bacteria. It's not enough just to have high numbers but only a few different types. You want to have lower numbers but a wide range of different types of bacteria. If you have diversity of bacteria, you'll have a lot more bacteria producing different types of health regulatory compounds, and the way to create a diverse microbiome is to consume a diverse diet.

You have to consume a wide range of different high-fiber foods because these are the foods that your bacteria require. The fibers in multi-colored vegetables especially, that's the number one food group for your probiotic bacteria. Then there's also multi-colored vegetables and various other types of foods that are high in fiber, but our human body cannot digest these fibers. They go through your system into your colon, your large intestine, and that's where your probiotic bacteria start to digest them. That's the food for your probiotic bacteria. Yes, it's important to take probiotics, but you have to learn how to feed your probiotic bacteria well. If you don't, they will not thrive and survive.

Here's a couple of examples of some other mechanisms and how they work on our behalf. Some probiotic bacteria produce a wide range of compounds called antimicrobial peptides. Scientists just abbreviate these as AMPs, but antimicrobial peptides are very small amino acid chains or I describe them as small fragments of proteins. They specifically have antibiotic effects, but they have a narrow range of effectiveness. They are only damaging to pathological bacteria. They don't harm your good bacteria whereas prescription antibiotics are called broad-spectrum. They kill everything, your good and your bad, but the natural antibiotics produced by your microbiome and your probiotic bacteria as antimicrobial peptides are only going to function or be active against pathologic organisms. It's an important part of your immune system. These natural antibiotics being produced in a healthy microbiome are sometimes suppressing the growth of any bad bacteria that happen to be resident in your gut.

Another example, there's lactobacillus fermentum ME-3. It's a very unique strain of probiotic bacteria that synthesizes glutathione. Glutathione is a postbiotic metabolite of that particular strain of probiotic bacteria. I could go on and on. There are many different types of postbiotic metabolites. Just a couple of general classes, your probiotic bacteria are little chemical manufacturing plants. They make all the B vitamins and Vitamin K and some of the critical amino acids. They make some of our most important nutrients. That's really a source of some of our nutrition. That's a little overview of some of the things and some of the ways that some of these other postbiotic metabolites are helping us.

Gazella: Yeah. Those are some great examples. I have to say, when I knew that I was going to talk to you about this topic, I jumped online to do a literature search and I was actually quite surprised at the amount of research specifically about postbiotic metabolites. Can you tell us about some of the more recent studies that you have enjoyed reading about in the scientific literature?

Pelton: Sure. Well I'm very excited having learned that a strain of bacteria called lactobacillus fermentum ME-3 can produce glutathione. Glutathione is one of the most important compounds in the human body. We call it the master antioxidant. It's produced in every cell in your body, and glutathione probably protects more of your body than all the other antioxidants combined. Glutathione also is the master regulator of all your detoxification. Being able to boost your glutathione levels by taking a strain of probiotic bacteria everyday is really a breakthrough in health and medicine. That's a pretty unique, new understanding of one particular strain of probiotic bacteria.

Another thing that's very exciting to me is that, last year in Japan, there was some independent research done on Dr Ohhira's Probiotics which is a brand of probiotics that's produced in a fermentation process that's different than all other types of probiotics on the market. The fermentation process used in the production of Dr Ohhira's Probiotics allows the final product to contain over 400 postbiotic metabolites. This is a real interesting, new viewpoint and insight into how probiotic bacteria work where you've got a probiotic, Dr Ohhira's Probiotic by brand name, that's produced in a multi-year fermentation process -- and I'll explain that in just a moment -- but the end product contains 400 of these postbiotic metabolites.

Let me explain this fermentation process and how these postbiotic metabolites are produced. We start out with big fermentation vats in a sterile warehouse. They start out with 12 strains of probiotic bacteria. Then they, at seasonally appropriate times, harvest and shred dozens of different types of organically grown foods: mushrooms, vegetables, seaweeds, fruits, and so forth. Then the bacteria get to grow and digest and ferment these foods for 3 years before the product is ready for encapsulation. During that 3-year fermentation process the bacteria in those fermentation vats are breaking down the food and producing this wide range of postbiotic metabolites.

With Dr Ohhira's Probiotics, we are not so much impressed by the probiotic bacteria we're delivering. We're really focusing on the delivery of these postbiotic metabolites. We get what we call rapid microbiome restoration because we're not just supplying somebody with bacteria in a capsule. We're directly delivering these postbiotic metabolites. Other companies that supply probiotics, you have a capsule with bacteria in it. Those bacteria haven't done any work yet. It's like a starter culture. When you take those bacteria, they have to go into your system, start to try to find the proper foods that they need so that their metabolic processes can begin to start to produce some of these postbiotic metabolites that are responsible for improving the health of the gastrointestinal tract.

But with Dr Ohhira's, we're directly putting in over 400 postbiotic metabolites. We quickly readjust the acid-base balance and suppress inflammation and start to heal the leaky gut or intestinal permeability problems and have some detoxification capabilities and start to work against some of the allergies that might be present in the GI tract. It's a very fast, rapid way of addressing gastrointestinal problems.

Gazella: Yeah. I'll disclose to our listeners that I actually have been taking the Dr Ohhira brand of probiotics for a lot of years actually now. I have been impressed with the product. You're telling me something very, very new though. I had no idea about the 400 postbiotic metabolites and this delivery of all these postbiotic metabolites. I've always loved the fermentation process and all the organic foods that are put in there in a 3-year period, and there's just so much that I love about the product. This kind of adds a new level of complexity to this particular product. I'd like to stay on the Dr Ohhira product just because I always like to clarify dosages and ... Now, how many strains, again, are in the Dr Ohhira product?

Pelton: There's 12 strains that we use to start the process, but again, I want to kind of emphasize that our product is really what we call a complete microbiome product because it doesn't just have probiotic bacteria. It's got probiotic bacteria plus some of the prebiotic food supply that was present in the fermentation process, and most importantly, it's got this wide range of postbiotic metabolites.

We just redesigned the packaging for Dr Ohhira's Probiotics, and on the new package, there are 3 different arrows that go in a circular direction. The 3 individual areas, the words inside the arrows say probiotics, prebiotics, and postbiotics. The postbiotic arrow is right front and center on the package. We're trying to emphasize to people the importance of this topic of postbiotic metabolites and Dr Ohhira's specifically delivering postbiotic metabolites. There is no other probiotic in the world that we know of that is produced in this multi-year fermentation process that allows the direct delivery of postbiotic metabolites.

Gazella: So as a result, do you dose this differently than you would a typical probiotic? Am I able to maybe use less? How do you handle the dosing of this?

Pelton: Sure. The recommended dosage is 2 capsules daily. I'll give just a little recommendation on some other uses of it. If people have food poisoning and it's very common when people travel, get some bad food, and get sick pretty quickly, then I advise them to bite and squeeze the contents out of Dr Ohhira's and swallow it that way because the capsule in Dr Ohhira's is a patented delivery system where the capsule actually stays hard in the harsh acid environment in the stomach and then it becomes porous in the more alkaline pH in the small intestine. So it preferentially releases the contents in the small intestine. But if you've got food poisoning, if you've got bad bacteria directly in your stomach, you want to bite the capsules, squeeze the contents out so it gets directly into your stomach and start to fight the bacteria locally in the stomach. I have people who chew 5 to 10 capsules and do it every 20 or 30 minutes, and it clears food poisoning out very quickly for most people.

Another thing to emphasize is that, in the fermentation process, the bacteria learn to grow and thrive and survive at room temperature. Dr Ohhira's does not need to be refrigerated. That's a very nice user-friendly part of Dr Ohhira's. Also because of this patented capsule design, you don't have to worry about food. It can be empty stomach, can be with meals, after meals, makes no difference. Main thing is everyday get them in. If I'm working with somebody that has Crohn's disease or colitis or irritable bowel syndrome, some of these really serious GI problems, I personally suggest they try taking 5 to 10 capsules daily, maybe 5 capsules twice a day for a period of 10 days or longer until you start to get improvement because you want to power these postbiotic metabolites and start to accelerate the change.

Some relatively new information, SIBO is a condition that is getting a lot more press these days, becoming more recognized as a fairly widespread condition. SIBO stands for small intestinal bacterial overgrowth where you have bad bacteria that normally reside in the colon, but they backed up into the small intestine and then they digest foods there. They're in the wrong location in the GI tract. They produce a lot of gas and bloating and diarrhea. So a lot of people with SIBO can't tolerate probiotics, but with Dr Ohhira's Probiotics, we're not primarily delivering probiotic bacteria. We're delivering the postbiotic metabolites. Many people on SIBO will find that Dr Ohhira's is very helpful.

Gazella: Interesting. An interesting note too, it doesn't taste bad. I've actually opened up the capsule and put it on a little part of my gum.

Pelton: I'm glad you brought that up, Karolyn, because that's another recommendation I make. There are a couple of dentists that make this recommendation, and I myself do it personally. Several nights a week at bedtime, I will take one capsule and bite it in my mouth and squeeze the contents out and swish it around in my mouth before swallowing it. This helps support a healthy oral microbiome. It helps to suppress gingivitis and periodontal disease and things like that. We're not calling it a treatment for these conditions. You're just trying to support the health of your oral cavity and a good healthy oral microbiome.

Gazella: Yeah, absolutely. Probiotic supplementation and probiotic science has really come a long way. There was a time when we thought that all you had to do is eat a little yogurt and you're good to go. Then there was the exciting research regarding prebiotics and synbiotics. Now, there's this topic of postbiotic metabolites. What does the future hold when it comes to this exciting area of study that seems to be moving quite rapidly?

Pelton: Well I think the future is in postbiotic metabolites because ... In fact, even pharmaceutical companies, drug company industry is starting to look at postbiotic metabolites and realizing that there's potential for them to develop new drugs on these naturally occurring compounds that are produced by your probiotic bacteria. These are compounds that are natural to the human body. It's not like they're putting a foreign chemical into your body.

As I mentioned earlier, Dr Mayer, in his book The Mind-Gut Connection. He's telling us that your probiotic bacteria produce hundreds of thousands of metabolites. I think the future will be less emphasis on just trying to name and identify strains of bacteria, but learn more about what are the compounds, what are the postbiotic metabolites that these bacteria make, what are the health regulatory effects of these compounds, which bacteria are more efficient at producing these compounds.

I think that's really the new area, new era, new frontier of microbiome research. It really is very exciting because we're really starting to understand that the microbiome is the foundation of your health at all levels. There's a physician by the name of Alessio Fasano who discovered the primary cause of leaky gut and intestinal permeability which happens when you have inflammation, it opens up your tight junctions in your GI tract and allows toxic things to leak into your system. Dr Fasano says that 2 main causes of inflammation and leaky gut are gluten and bad bacteria. I recommend that everybody be on a gluten-free diet. Then we need to clean the gut up.

I did a presentation a month ago at the American Association of Antiaging Medicine Conference, and my topic was Natural Therapies for ADD and ADHD. One of my primary messages is scientists are looking for the answers for autism and ADD and ADHD in the brain. Don't look in the brain. The answer is in the gut. We have to heal the gut and heal this intestinal permeability problem because if you have leaky gut, you have leaky brain. We mean your blood-brain barrier is leaky and some of these toxins are getting into your brain. You have gut inflammation. You have brain inflammation.

We have to focus on the gut, and one of the most serious worldwide health dilemmas right now is the rapid rise in antibiotic-resistant bacteria. Many of the people listening to this probably are familiar with MRSA, methicillin-resistant Staph aureus. There's hardly any antibiotics that are effective against it anymore. Now, we've got antibiotic-resistant [inaudible 00:29:33] and antibiotic-resistant tuberculosis on the rise. We have to understand that we have to reduce our reliance on antibiotics and increase our reliance on good bacteria. We need more bugs, not drugs.

The rise of antibiotic-resistant bacteria is a global health crisis, and you don't want to have a weak immune system and wait until you get sick because scientists are talking about a postantibiotic era where antibiotics are not going to be effective anymore. We won't be able to have Cesarean births and we won't be able to have our appendix out or our teeth cleaned because, if you get an infection, you're dead. The answer to the problem is to have a good healthy diet with lots of fiber-rich foods to create a diverse microbiome which gives you a healthy immune system. That's the way to stay away from all these antibiotic prescriptions. That's my little rant on that topic.

Gazella: No. It makes a lot of sense. I have to say that human microbiome research is fascinating and so important. This new research on postbiotic metabolites resulting from probiotics just really adds a lot to the conversation that we need to have about -- excuse me -- the human microbiome. Don't you agree?

Pelton: I agree totally. I think this is the next level of understanding of how and why the microbiome is important and gives people a little bit more insight into why it's so important to learn how to create and maintain a healthy microbiome so you can have many different types of bacteria producing all these health regulatory postbiotic metabolites so that, in turn, you will have a healthy immune system.

Gazella: Absolutely. Well this has been a great interview with a lot of great, important information. Once again, I'd like to thank the sponsor of this interview who is Essential Formulas Incorporated. Thank you, Dr Pelton, for joining me today.

Pelton: My pleasure. Nice to be with you, Karolyn.

Gazella: Have a great day.

Pelton: You bet. Bye-bye.

About the Author

Natural Medicine Journal is an electronic peer-reviewed journal and open access website dedicated to the field of integrative medicine.