Research is confirming that there is a direct link between the gut and the brain. In this interview, probiotics expert Ross Pelton, RPh, will describe the research associated with probiotics and brain health. The focus of the interview is on cognition and mental health issues such as depression and anxiety and how probiotics may help patients with brain issues.
Approximate listen time is 31 minutes
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 1 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.
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're talking about the gut-brain axis and how probiotics can help with brain function, including mental health issues and cognition. Before we begin, I'd like to thank the sponsor of this topic who is Essential Formulas Incorporated. My guest is probiotics expert and registered pharmacists, Ross Pelton. Ross, thank you so much for joining me today.
Ross Pelton: Hi, Karolyn is really nice to be with you and your audience again. Appreciate it very much.
Gazella: Yeah, this is a really interesting subject. We've covered it a little bit in the Natural Medicine Journal, but I'm really anxious to kind of dig in a little bit more deeply with you. So let's just jump right in. How much do we know about the connection between what's going on in the gut and how that can influence the brain?
Pelton: Well, we're starting to learn a lot more about it and I would say that we're still in the infancy of this learning curve, but we now understand why we call the gut your second brain. There's an enormous amount of neurons in your gut. There's over a hundred million neurons and your probiotic bacteria and the compounds they produce, interact with those neurons in your gut and send signals to your brain up what's called the vagus nerve, and so that's how the gut communicates with the brain, through this super highway of nerves called the vagus nerve. It's the longest nerve in the body. What's really interesting to me, Karolyn, is that they've figured out that about 20% of the vagus nerves are sending information from the brain into the stomach or the gut. But 80% of these nerve fibers in the vagus nerve are sending information from the stomach to the brain. So the majority of this information, this communication between the gut and the brain is really the gut communicating with the brain.
Gazella: Wow. That's pretty cool. So let's talk a little bit about the scientific literature then. What does the scientific literature tell us about the link between the gut microbiome and mental health issues like depression and anxiety?
Pelton: That's getting to be a big topic also and there's a tremendous amount of work being done in that area. In the cover, on the cover of the magazine Psychology Today, in April, 2014 their lead article was the psychobiotic revolution, how your gut bacteria control and influence your emotions and your state of mind. So a mainstream journal, Psychology Today, is referring to what they call a psychobiotic revolution. There's more and more studies that are starting to tease out how this happens. One study I found that was very interesting, mice who were infected with a very small of a toxic bacteria called campylobacter, but it was such a small dose, it did not cause any immune system activation. So the body really didn't know it was there. There was no immune alarm reaction.
However, several tests revealed at the mice exhibited greater levels of depression and anxiety-like behavior. So the brain knows, even though the body wasn't responding with an immune reaction, the brain could tell that there was some bad bacteria, very small amount in the gut. In a human trial, it was chronic fatigue patients. It was a placebo controlled trial so some of the chronic fatigue patients were getting probiotics and some were getting a placebo and they did stool samples and they did a number of tests of depression and anxiety and the people taking probiotics were calmer, had less anxiety and claimed they were better able to cope, they got better sleep and they had fewer heart palpitations. So animal studies and human trials are also kind of combining to give us more and more information about this gut-brain communication.
Gazella: Great. Now what about other brain issues like cognition and concentration? Does the gut-brain axis cover those issues in the scientific literature as well?
Pelton: Well, it really does and it starts at birth and there's a real strong and important relationship between the early microbiome and child cognitive development. You find out that when children are born with a Cesarean birth, the mother has to give a C-section birth, then there's a difference in the microbiome. They've studied infants between C-section births and healthy natural vaginal births and they find out that the infants that are born via C-section for cognitive development through the ages of 4 through 9 is what this particular study looked at and they called it a cognitive gap. So it's just more information that's detailing that an infant's microbiome plays a real critical role in cognitive development.
Now, we're learning more and more about the relationship between microbiome and psychology and neuroscience and normally you'd think that the fields of psychology and microbiology are not really connected, but now they're starting to be strongly connected because we're finding out how strongly microbiology and the influence of your bacteria communicate with your brain and affect your mental, emotional states. So gut health affects mental health is the stronger and stronger message that's coming out from the scientific community.
Gazella: Yeah, it's really true. I have to tell you, there was an interesting study that I read while I trying to prepare for this interview and it was involving traumatic brain injury. Now, I understand that that connection is preliminary, but it's pretty promising to make the connection between traumatic brain injury and the gut. How can probiotics help someone who has experienced traumatic brain injury?
Pelton: Well, there's several studies that have been done on this now. The gut-brain axis is a communication between the gut and the brain and it's the nervous system that does the communication, and when you upset the nervous system, you're going to upset the communication between the gut and the brain. So the gut microbiome has a central role in this pathway of humidification and it's really altered. They find out that the gut microbiome is significantly altered following a brain injury. It reads to more inflammation in the central nervous system and that affects the brain. You get brain inflammation. So that's 1 of the studies that talked about this traumatic brain injury microbiome relationship.
In animal studies, it's not nice to talk about these studies because they do some nasty things to the animals, but that's the way we learn about a lot of these things. So they took some male rats and divided them into 2 groups. One group received a brain injury and the other didn't. But they looked at their microbiome before and after and they started a pre-traumatic brain injury incident and then they rechecked the microbiome in day 2, day 7, and day 14. They found that the mice that had received the traumatic brain injury, there was a definite significant change in the composition of their microbiome and it got worse as time went on. They started looking at the microbiome before the injury and then checked it at 2 hours after the injury and then 1 day, 3 days, and 7 days afterward. The change in the microbiome continued to worsen after that traumatic brain injury. So when we learn more about this, we see that the faster you can intervene, the more help that you can provide in this type of a situation.
Gazella: So the scientific literature is clear that in cases of brain function, mental health, like depression, anxiety, and even in cases of traumatic brain injury, that the gut microbiome is altered. Does the scientific literature tell us that a probiotic intervention can reverse, change or influence the gut microbiome in such a way that the brain will be positively influenced?
Pelton: Well, yes. That's what we're learning is that if you supply probiotics, you will change the gut and you change the electrical and chemical communication between the gut and the brain and you can influence the brain in positive ways. There's a number of researchers that are really documenting the changes in the brain from microbiome probiotic administration. There's a scientist by the name of [Christine Tillich 00:09:11] and she does brain imaging scans on people, these are human clinical trials. She had a group of women who had no previous gastrointestinal complaints and no previous psychiatric problems. She gave them probiotics twice a day for 2 weeks and she conducted functional MRI brain scan on these women and they were looking at the brain activity when the volunteers were viewing faces that contained different emotional expressions and they found changes in the brain regions that control the central processing of emotions and sensations.
So this is a placebo controlled trial. Some of the women who were taking something but wasn't a probiotic and then the other women had probiotics and the women that had probiotics, they found positive changes in the brain areas that process emotions and sensations. So really interesting work that's being done.
Gazella: Yeah. Very exciting to know that we have this intervention. Now, last year I read about a very small study that got some publicity and it was actually negative towards probiotics and it stated that probiotics can actually cause brain fog. I'm not sure if you had a chance to read that study or what's your take on this issue if it's come up in your pharmacy practice that probiotics can actually cause negative brain issues?
Pelton: Well, I'm familiar with that study and my take on that is that this has to do with SIBO, small intestinal bacterial overgrowth. When people have SIBO, then yes, probiotics can cause a problem because SIBO is a situation were bacteria that are normally resident in the large intestine and the colon have translocated. They backed up into the lower portion of the small intestine. So it's not necessarily bad bacteria, but it's just bacteria that are now in the wrong geographical location in the GI track. Those bacteria can digest the fibers in food and cause gas and bloating and a great deal of discomfort. They produce a compound called D-lactate and that can produce brain fog.
But the scientist that reported this, I think, really didn't report it correctly, or at least how I would like to report it because he's just saying that taking probiotics cause brain fog. Well, you have to understand that this is in SIBO and many people with SIBO should not be taking probiotics because the bacteria will digest the fibers and cause a great deal of gas and bloating and discomfort. So SIBO is a unique situation and needs to be dealt with separately.
Gazella: Yes. Now, that makes a lot of sense. I'm glad that you clarified that. So when it comes to using probiotics in clinical practice for brain health, do you recommend probiotics as a sole treatment or as a part of a more comprehensive protocol? How can clinicians best use probiotics in clinical practice for this particular application?
Pelton: Well, I'm always in favor of a more comprehensive approach to health, so I wouldn't advocate just probiotics. It's really important to understand how important a healthy diet is and exercise and good sleep. I also advocate a wide range of different types of nutritional supplements. But probiotics are 1 of the things I do recommend on a regular basis and it's kind of like insurance where you might not need it, but if you get in this situation where you need it, you're darn happy that you have it. I would say that there's certainly a range in how important probiotics are to people. Some people can maintain a microbiome when they're eating a healthy diet and they do pretty well long term and they might be less in need of probiotics on a regular basis.
But I would say the majority of Americans, in fact, I've got 1 study that said that 90% of adults and children in America do not consume the recommended amount of fiber in their daily diets and fiber is what feeds your good bacteria. So if you're not getting adequate fiber in your diet, then you're not supporting the growth of your microbiome and your need probiotics. But I really emphasize the people, Karolyn, probiotics alone are not enough. You have to feed your probiotics well, otherwise they won't thrive and survive. So it's a combination of a fiber rich diet with lots of fruits and vegetables, especially the multicolored vegetables. That fiber will feed your microbiome and promote growth and proliferation of a more diverse microbiome. So it's probiotics plus fiber in the diet.
Gazella: How do you counsel your patients about getting more fiber in the diet? Because I think you're right. I think that this is a big issue and the statistics are pretty clear that people aren't getting enough fiber and fiber and probiotics go hand in hand. How do you teach them to get more fiber in their diet?
Pelton: Well, I encourage people to Google my YouTube video. It's an 8-minute youtube video, just Google Ross, R-O-S-S, and and salad buzz, B-U-Z-Z. It is an 8-minute video that I teach people how to save a lot of time making salads. One of my theories is that people don't eat salads often enough because they're time consuming. But I teach to process all the vegetables all at once and then the secret to the whole process is squeeze a lemon over all of your processed vegetables and toss that lemon and lemon juice in your vegetables and the vitamin C in the lemon juice will preserve your precut vegetables. So I put it in a Tupperware and it stores easily for a week and then every night when my wife and I have our big salad, I take a handful of lettuce and a handful of vegetables that I've already processed and put some wild caught salmon on there. It takes me like a minute to make supper. So it's a way to get a wide range of vegetables because I've got about 14 different types of vegetables in my salad mix and it saves time in the process.
Gazella: Yeah, it's a great idea. I'm sure that practitioners may want to share that with their patients. So that's Ross salad buzz. Go ahead and search that. So now let's talk about probiotics. I mean, this is a field where there are a lot of different types of probiotic products. So what do you feel clinicians should look for when choosing a probiotic to recommend to their patients?
Pelton: Well, that's a really broad topic, Karolyn, and there's a lot to talk about there. Turns out that humans have somewhere between 500 and a thousand different species of bacteria in their GI track and we're just beginning to learn what these are and there's a wide range between your microbiome and my microbiome. But generally you want to have a strain that has been prepared well in manufacturing so they good shelf life. That's a critical factor whether or not they need to be refrigerated. But 1 thing I'd like to talk about is what I call the new frontier in microbiome science. This is the term postbiotic metabolites. Now, some of your listeners might not be aware of this term, but it's really in 1 of the most important new understandings about probiotic bacteria and the microbiome.
We're starting to learn that it's not so much the bacteria that are important, but it's the compounds they produce and we call these compounds postbiotic metabolites. So the process goes like this. You ingest fiber rich foods, your probiotic bacteria break down those fibers and produce secondary compounds that we call it postbiotic metabolites. These are the compounds that are the master health regulating compounds for the entire body. These postbiotic metabolites influence the functioning of every single organ system in the body, especially your immune system in your brain. I use the analogy of NASA's mission control center, controls our space flights. There's dozens and dozens of scientists and engineers but it's really the hundreds of computers making millions of decisions every second that guide and regulate our space flights.
So in my analogy, your probiotic bacteria are kind of like the scientists and engineers, but it's your postbiotic metabolites that are really doing all the work, controlling and regulating all the signals that are having an effect on virtually every single organ system in your body. So that's the real important message and the new frontier and the microbiome, learning what bacteria produce these compounds, what strains of bacteria are more efficient at producing some of these compounds and as we get farther into this whole topic, science will start to tell us what types of fibers and what types of food will primarily or preferentially feed different types of bacteria.
We know that diversity is important for a healthy microbiome and that means a wider range of different types of bacteria. The way to get a wider range of different types of bacteria is to consume a wider range of different types of fiber. So it's not just the quantity of fiber, it's also the the different diversity, different types of fiber is what's required to get a diverse microbiome.
Gazella: Now give us some examples of the postbiotic metabolites that are produced that are so important to our health.
Pelton: That's a big topic and I'm glad you've asked me because it's fascinating to me. Our probiotic bacteria are fascinating little chemical factories and so some of the postbiotic metabolites, all the B vitamins are produced by your probiotic bacteria. Several of the amino acids, they make a lot of the neurotransmitters and lactobacillus fermentum ME-3 produces glutathione. Some of the strains produce hydrogen peroxide, which is active against some of the things like Candida yeasts and short chain fatty acids are 1 of the big, most important categories that we know about. These short chain fatty acids are active against pathogens. They rebalance the acid base level. They have antiinflammatory activity. So that's why these postbiotic metabolites are so important because these are the compounds that have all the activity to regulate the microbiome ecosystem.
So again, it's not just the bacteria, it's all these compounds that they produced. These compounds are produced during fermentation. The bacteria ferment foods to get access to the fibers and then they change these fibers into these secondary metabolites, the postbiotic metabolites. So fermentation is the process that creates the postbiotic metabolites. For years, and in fact for centuries, fermented foods have been a primary way that we preserved foods and it's the postbiotic metabolites, especially the short chain fatty acids that are produced during fermentation that create an acidic environment to suppress the growth of pathogens. So that's how fermentation works and that's an important part of your immune system because in your gut, the bacteria go through fermentation process and produce these short chain fatty acids that will suppress the growth of pathogens.
Gazella: Yeah. When you're describing this, you're describing this combination of fiber plus bacteria. So you're actually describing more than a probiotic. You're describing more of a whole food extract or what's sometimes called a symbiotic. Is this where we're headed? It seems like there's not a lot of probiotic products that have fiber rich foods combined with the bacteria to create this whole food combination, which then creates the posts by attic metabolites. So it seems like this is unique.
Pelton: Well, you're right. Although you will see some probiotic products that have a prebiotic in them, like fructo-oligosaccharides or FOS. I mean, some of them had things like inulin in them. But keep in mind, we want to strive for a diversity of fibers and so these products just have one type of fiber or 1 or 2 types of fiber. A product that I'm very familiar with because I'm the scientific director with Essential Formulas is called Dr. Ohhira's Probiotics. They're made in a fermentation process. It takes years to produce the product. They have large fermentation vats where they start out with 12 strains of bacteria then they had dozens of different types of organically grown foods and the bacteria are given 3 to 5 years to break down and ferment all of these foods, and during the process they're producing a wide range of postbiotic metabolites and scientific research has determined that Dr. Ohhira's Probiotics contain over 400 different postbiotic metabolites.
So Dr. Ohhira's is really not primarily a probiotic. It's primarily delivering postbiotic metabolites directly and it's a much faster way of effecting change in the microbiome because if you just take probiotic bacteria, those bacteria, when they reached the gut have to find fibers and begin the process of breaking those fibers down and transforming them into the postbiotic metabolites. But Dr. Ohhira's is directly delivering these postbiotic metabolites so you get a really rapid microbiome restoration because they immediately, as soon as they hit the gut, they start to produce the antiinflammatory effects and accelerates the regrowth of healthy new cells that line the GI track. It's just a really unique fast way to create change and correct things like dysbiosis.
Gazella: So you mentioned that there are dozens of forwards in the Dr. Ohhira's product that are fermented and combined with the 12 strains. What are some of the types of foods that are in that product?
Pelton: They have a wide range of fruits and vegetables and mushrooms and seaweeds, all healthfully raised. They have different standards in Japan, so they're not what we would call organically grown by our standards because they just don't have those standards. But they're healthfully grown. They use pure spring water. There's no pesticides and insecticides and artificial fertilizer or anything, and they're allowed to grow naturally and then there are harvested at their peak of ripeness. So the nutritional content is at its peak and then they shred these foods and add them to the fermentation vats so that the bacteria can start to break them down and do the fermentation process that allows them to produce the postbiotic metabolites.
Gazella: Now you mentioned that you don't have to refrigerate Dr. Ohhira's. I mean, as a consumer, I actually find that really appealing, but some practitioners are pretty focused on the refrigerated probiotic products. Why don't you have to refrigerate Dr. Ohhira's?
Pelton: Well, Dr. Ohhira's, this fermentation process that I've spoken about, the bacteria learn to thrive and survive in the fermentation vats at room temperature. So they have adjusted to survive in a room temperature and then the capsule for Dr. Ohhira's Probiotics is a patented capsule design that's as hard in the harsh acidic environment in the stomach and then preferentially releases all the contents in the small intestines. So it's a user-friendly product where food is not an issue, it could be taken on an empty stomach or with food and refrigeration is also not an issue.
Gazella: Then what's the dosage of the Dr. Ohhira's if you're just going with regular maintenance and there's not really a therapeutic application? You just want to recommend it to your patient for optimal health.
Pelton: Sure. The recommended dose is 2 capsules daily on a ongoing regular basis.
Gazella: Perfect. So I'd like to talk a little bit about the future because it sounds like what you've just described with this whole food extract and this fermentation process at room temperature and the paste that's created and it's put into this special gel cap that can survive the stomach. It sounds like that we're headed to the future. So bring out your crystal ball and tell us 2 things. First of all, what does the future hold when it comes to probiotic research and advancement and then what does the future hold when it comes to this gut-brain axis and where we're headed with that?
Pelton: Okay. Well, I think that in the future we'll see more and more recognition of the benefits of these postbiotic metabolites. I think more companies will start to try to develop products so that they can directly deliver postbiotic metabolites. In fact, the pharmaceutical industry also sees the handwriting on the wall. I've looked at a number of different reports where pharmaceutical companies are starting to develop new products that contain postbiotic metabolites. The pharmaceutical industry realizes that rather than trying to develop more antibiotics, they can start to develop products that contain postbiotics and these new products will be less expensive to produce. They'll have fewer side effects because these are compounds that are naturally produced in the human body. So it's a new frontier for the pharmaceutical industry also. The postbiotic metabolites is a new frontier all the way around.
Your other part of your question is how do I see the whole industry of probiotics going? We'll continue to discover new strains of bacteria, but I think there will be more emphasis focused on trying to discover what are the compounds, these postbiotic metabolites, the different strains of bacteria produce. So it's not so much trying to just discover different strains of bacteria and name them, but what are these compounds that they're producing and which strains of bacteria are more effective at producing these compounds for us. I think we'll also get into in the future much more personalized microbiome understanding so that different people will react differently or more favorably to different types of probiotic products and even different types of postbiotic metabolites will probably be more effective and more important for different types of individuals with different types of problems.
Gazella: Yeah. I have to say that this does lend itself to that personalized medicine that practitioners and researchers are talking about. So I would agree. I think that's a great direction to go in. Now when it comes to the gut-brain axis, I know a lot of the research that we talked about today is a bit preliminary. Are you expecting to see some more formalized larger clinical trials, human trials, double-blind, randomized placebo-controlled trials in the area of mental health, potentially dementia, Alzheimer's, concentration, maybe chemo brain? I mean this is just such a big topic.
Pelton: Well, yes, Karolyn. That's another huge frontier for the microbiome. Some studies are calling the microbiome the missing link in the gut-brain axis and they're starting to focus more on the microbiome's role in the link between gastrointestinal health and mental health. So we'll see a lot of that happening in the future. I can share 1 study with your listeners that's really quite amazing that talks to the mental health issue and the relationship between the microbiome and mental health. Scientists started out with 2 strains of mice. One strain of mice is specifically bred to be highly timid and anxious and the second strain of mice are bred to be highly courageous, bold, and exploratory. So then the researchers just took the bacteria from the GI track of each strain of mice and implanted them into the opposite strain.
It completely reversed their behaviors, just by changing the bacteria and their microbiome, taking it from the bold, courageous exploratory mice and transplanting those gut bacteria into the strain that was timid and anxious. It just totally changed the behavior from being bold and exploratory to being timid and anxious and did the reverse in the opposite of mice. So fascinating information to see how just the gut bacteria have this direct influence on behavior and emotional activity and so forth. I'm sure we'll see many more studies in the future that are starting to unravel how this all works for us.
Gazella: Yeah, I would agree. This is going to be fun to keep an eye on and to follow because it's really exciting and it can really make a difference in patients' lives. So once again, I'd like to thank the sponsor of this topic was Essential Formulas Incorporated, of course, the distributors of Dr. Ohhira's Probiotics. Thank you, Ross, for providing us with such a great amount of interesting information for us to consider. Have a great day.
Pelton: Okay, Karolyn. Nice to be with your listeners. I want to just encourage everybody, every time you eat, you're feeding 100 trillion guests, so feed your probiotics well.
Gazella: Absolutely. That's great ending advice. Thank you.
Pelton: All right.