The Gut-Brain Axis with Dr. Jeff Moss

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In this podcast, I discuss the gut-brain axis with Dr. Jeff Moss.  This was a fascinating conversation about the latest research on the connection between gut microflora and it’s intimate connection to the brain and nervous system.  We talk about this connection with neurotransmitter imbalances, autonomic nervous system dysfunction, Alzheimer’s disease, Autism, gut healing strategies and much more.

Dr. Jeff Moss

Here is the transcript of my conversation with Dr. Jeff Moss on the Gut-Brain Axis:

Dr. Hedberg: Okay, well, welcome, everyone. This is Dr. Hedberg, and thanks for tuning into “The Dr. Hedberg Show.” I’ve got a very special guest today, Dr. Jeff Moss. And Dr. Moss is a graduate of the University of Michigan Dental School 1974. He practiced dentistry in Grand Rapids, Michigan until 1985. And he employed clinical nutrition in that practice, and he decided to use that experience and enter the professional supplement industry.

So, for the last 24 years, Dr. Moss has operated Moss Nutrition, which supplies the Moss Nutrition professional line of supplements to practitioners. And, since 2000, he has served as adjunct faculty at the University of Bridgeport Nutrition Institute, starting with the vitamins and minerals class and most recently adding the assessment in nutrition class to his teaching responsibilities.

He’s co-authored the textbook, the “Textbook of Nutritional Medicine” by Dr. Melvyn Werbach, and Dr. Moss was president of the International and American Associations of Clinical Nutritionists from August 2000 to June 2001.

Moss Nutrition’s website is mossnutrition.com, and those of you who are patients of mine know that I’m a big fan of Moss Nutrition products because of the quality and because of all the research behind their products, and just fantastic customer service, and just a great company to work with across the board. So Dr. Moss has definitely been a mentor of mine. He’s one of the only doctors out there in the functional medicine world who I listen to and respect, so I’m really excited to have him on. Jeff, thanks for joining me.

Dr. Moss: Well, thanks so much for having me.

Dr. Hedberg: So today we’re gonna be talking about the gut-brain axis. This is a topic that is kind of sweeping the functional medicine landscape with good reason. We’ve been addressing this issue for a long time, but we’re learning more and more about how the gut flora affect extraintestinal aspects of the body, and the brain, and the rest of the body system. So why don’t we jump in, and can you just talk a little bit about how the gut microbiota actually interact with our nervous system?

Dr. Moss: Sure, there are really several different ways that it does it, and before I get into all of the ways, I guess the big picture here is that why this is so interesting and why it is important and so exciting is, because of the way we’ve traditionally viewed any type of central nervous system issue, either behavioral or neurodegenerative, we’ve kind of viewed as the central nervous system kind of hanging out there in space. We view the blood-brain barrier as basically impermeable to a lot of different things, and because of that the way we viewed it and the way we intervene was basically looking at it directly. There really wasn’t connected to anything else in the body.

And I remember I got this very early on as a dentist. You know, the head is just kind of detached from everything else from a physiologic and mostly in terms of a diagnostic and clinical interventional therapeutic standpoint, and so I think that’s the big picture here before we get into the complexities even if some of it’s a bit difficult to understand. The big picture here is that the brain is incredibly influenced by what else is going on in the body, and particularly what’s going on in the gut. So, with that in mind, there are really several different ways.

Number one is what is classically known…we have neuroanatomical pathways, the autonomic nervous system, the vagus nerve, the classic anatomy, and the gut flora can have a direct impact on that, but really that’s only the beginning. It also can have impact on stress physiology, what is known as the hypothalamic-pituitary-adrenal axis.

Research shows that gut microflora…and I’ll talk about how it does that in just a second, but it has an impact on stress physiology, the endocrinology, and the pathways involved, and how we respond to stressors. There, of course, is the immunologic impact. Gut microflora have a direct impact on the immune system in the gut, and most immune cells are in the gut, but beyond that, there’s kind of a ripple effect where it has an impact on systemic immunity.

And the reason that is important, we now understand that behavioral and neurodegenerative illnesses are primarily inflammatory, that there is a neurologic immune system mediated by some cells in the brain called microglia. They’re like inflammatory cells, if you will, like an inflammatory cell, like a lymphocyte or a neutrophil, but it’s in the brain. They call them microglia, and gut microflora can upregulate activity of this microglia the same way they might do it systemically with the white blood cells we’re all familiar with. So that’s another way that it can do it.

It also has an impact on the blood-brain barrier. What I mentioned before, this idea that it’s kind of impermeable, well, it will have an impact on the blood-brain barrier and may basically make it more permeable. We know that imbalances of gut microflora, for example, will affect the gut barrier, creating leaky gut. Well, the gut microflora can also create leaky brain, for lack of a better term.

The factors that are involved in terms of creating this scenario, gut microflora are responsible for producing short-chain fatty acids, and from a positive aspect, these short-chain fatty acids are well-known to butyric acid can improve the health of the gut lining. But there are other short-chain fatty acids, again, pre-produced, and when there’s an imbalance, these short-chain fatty acids can actually get into the brain. If there’s a leaky gut, they circulate, go through the leaky blood-brain barrier, get into the brain and cause disturbances in that way.

They also produce something that most of us aren’t familiar with, GABA, gamma-Aminobutyric acid, which can have an impact. Another big way that the gut microflora interact, as most of us know, we all know about serotonin, and we tend to think about serotonin as a central nervous system issue. We’re all familiar with SSRIs for depression. Well, in actuality, most of the serotonin is not produced in the brain. When you look at the total body production, most of it is produced in the intestine, and gut microflora, when there are imbalances, can affect the serotonin production in the gut. And this is fairly well-known as being related to…contributing to IBS, constipation, different types of IBS manifestations. But we now know that the serotonin produced in the gut, which is influenced by gut microflora, can also affect the central nervous system. It’s not just a systemic IBS-type scenario.

Finally, I did wanna talk a bit more about its impact on the vagus nerve. This is significant. And the vagus nerve, of course, as we know from our anatomy days, this is a very large nerve that has several different functions, part of which relate to the gut. But, again, this can have systemic manifestations also.

Dr. Hedberg: Yeah, and one of the things that I see very frequently in practice which ties in with everything you just talked about links to early adverse life events. And if we go back to childhood and we look at antibiotic usage at a very young age, and not just antibiotics, but not being breastfed, C-section, poor diet, and then all those psychological and physical traumas that people can go through as a kid.

There are so many connections there kind of setting someone up for some difficulties later in life, not just with their microflora, but with mood disorders, and irritable bowel, SIBO, inflammatory bowel, and things like that. Did you have anything to add to that regarding early adverse life events and a disrupted gut-brain axis?

Dr. Moss: Yeah, you make a very good point. For about 100 years now, we’ve been conducting this uncontrolled experiment on manipulation of our microbial environment, both in the world around us and the world inside of us. Antibiotic use is about 100 years now, and it starts, of course, for most people in terms of direct administration, some people, as you say alluded to, very early on. But when you look at the antibiotics in the food supply, it probably starts in utero, before birth.

And so, yeah, you make a very good point, that in our society after a 100 years of antibiotic use, we have created some disturbances in our gut microflora let alone the microflora world around us. Now, unfortunately, this, of course, is not all black and white. Am I saying that we shouldn’t have had antibiotics? History of infectious disease suggests that there’s a lot of benefit, and I’m not going to argue against that for a minute.

There are certain scenarios of certain types of bacterial infections, and certain populations, certain individuals, particularly very young and the very elderly, where antibiotics have definitely…the benefits have definitely outweighed the risks. What’s the problem, I think, is we have seen gross overuse and misuse.

If they were used the way that they intended in the ’20s, when penicillin was first discovered, limited occasional use for significant bacterial infections, I don’t think we would be having this conversation that we’re having today, or we’d have this conversation, but it would’ve taken a very different path. It’s the overuse and the misuse that has really put us where we’re at. So I’m not condemning antibiotics. I’m condemning poor decision-making about antibiotic use.

Dr. Hedberg: Right. Right, exactly, yeah, giving antibiotics for viruses, and they’ve definitely been overprescribed, but, as you said, we definitely needed them. So I mentioned a few illnesses mainly related to the gut, but can you talk a little bit more about all the illnesses that could be impacted by an abnormal gut microflora?

Dr. Moss: Yeah, there’s some very interesting research on this. Autism, of course, is probably the illness that may come to mind first for a lot of people, this whole very controversial idea of a connection between the gut and autistic disorders. And there is good research that suggests that disturbances in the gut microflora are going to have an impact. I think where the controversy lies is that many researchers are kind of looking for a one size fits all approach to it, that unless we can demonstrate that it causes or is a contributing factor to all autism that it’s a non-issue.

It appears that many in the mainstream and the research community simply cannot accept the idea that even if it contributes to autism in, say, 10% of the population, well, that’s still significant. Particularly if you’re a practitioner who’s dealing with one person at a time and even more importantly if you’re a parent who is dealing with their child, 10% means a lot.

So I understand where researchers are looking at it as a numbers game. But the fact remains in that there are… Research is clear that in certain autistic individuals, and, of course, this is where assessment comes into play, it’s not gonna have an impact on all of them, but certain patients, gut dysfunction, specifically as it relates to microbial imbalances, could be a significant causative factor.

Now, does that mean that if we balance microflora that the autism goes away? Well, not necessarily. You’re saying just because you took the knife out of the wound doesn’t mean the wound heals, but it’s a good start. And other interventions, of course, have to be introduced, both biochemically, psychologically, behaviorally, to help the autistic patient. But by removing or, I would say, optimizing gut microflora in the selected population where it is an issue, it can contribute to helping that patient. Again, it’s not the only thing, but it can be very helpful. So autism is very interesting. It’s not the majority, but it will be a small but significant population.

There’s some other research that looks at… I found research on MS, multiple sclerosis, and, of course, which is a classic neurodegenerative autoimmune disorder. And I think any time we have any type of autoimmune disorder that, whether it be systemic or neurologic, we really do have to take a look at the impact of the gut generally and the gut microflora specifically. It’s going to have an impact on… Those imbalances of gut microflora will alter the immune system anywhere in the body.

The idea that gut microflora seem to be inhibited or regulated by classic compartmental walls, if you will, whether it be the gut lining or whether it be the blood-brain barrier or any other type of anatomic barrier or biochemical barrier that we’re classically familiar with, the reality is that the gut microflora, either through direct impact or more often the production of what they call lipopolysaccharides… And what are lipopolysaccharides? Basically, it’s microflora excrement is what it is. Everything that lives excretes. And this excrement of certain types of organisms, when there’s imbalance, can circulate throughout the entire body and will have an impact on immune function anywhere in the body and so would make sense that we’re gonna see an impact with multiple sclerosis.

But some of the most interesting research that I found is Alzheimer’s disease. Alzheimer’s disease, I think, if you interviewed, I’d say, a large population of baby boomers what do they fear the most, interestingly enough, it probably is not death, although they may say that. What they fear the most is dysfunction, it’s not being able to do the things and be a contributor to society.

It’s one thing to have dysfunction in terms of you can’t physically do the things you want to do, but losing mental capacity, recognition of even loved ones is maybe one of the biggest fears. And so it’s a big issue, and this immunologic connection, Alzheimer’s disease it’s only now has begun to be fully appreciated. And, just like I talked about with any other illness such as MS, if you have an immunologic connection, the gut microflora will play a part, and so Alzheimer’s disease attracts a lot of attention in this area and deservedly so.

Dr. Hedberg: Yeah, and I’m glad you brought up lipopolysaccharides, because normally those are kept in check in the gut because of tight junctions. But when patients develop dysfunctional gut and they get a leaky gut, also known as gastrointestinal hyperpermeability, they get into the bloodstream, and then they can get through the blood-brain barrier. And that’s why so many people report things like depression, and anxiety, insomnia. Any kind of mood disorders sometimes will significantly get better just by working on healing the intestinal tract and the lining. And so that’s a great explanation of all that, plus the things you’ve talked about before, the autonomic connections there with the vagus nerve and the enteric nervous system.

Dr. Moss: Yeah, you bring up, I think, an important area. I did mention behavioral disorders such as depression, anxiety. I didn’t find a lot of research on it. But, with that said, there is a tremendous amount of information on the impact of inflammation and depressive disorders. Mainly because of its impact on what is known as the kynurenine pathway, tryptophan metabolism, inflammation can grossly alter this.

And while, like I said, I couldn’t find a lot of information directly linking gut microflora and behavioral disorders, logical extrapolation suggests that, like I said, if depression indeed is inflammatory, in many patients it is, and if the patient demonstrates significant GI dysfunction, and a history of antibiotic use, and other things that would strongly suggest gut microflora dysfunction, as you said, from a clinical standpoint, even though we may not be able to produce a lot of double-blind placebo-controlled studies, it would make logical sense to really address gut function when addressing behavioral disorders.

Dr. Hedberg: These neurodegenerative disorders are obviously on the rise, Parkinson’s, Alzheimer’s, and you mentioned Alzheimer’s before. Can you give some more details on Alzheimer’s and that relationship with the gut microflora?

Dr. Moss: Yeah, there are three main factors that have to be looked at with Alzheimer’s disease. I talked about one, inflammation. The other one is poor insulin metabolism. Insulin resistance is considered to be a major issue. Disturbances in glucose metabolism in the brain, which can be created by systemic insulin resistance, and certainly inflammation. It’s a vicious circle, and systemic inflammation can cause insulin resistance and vice versa. It’s a vicious circle in that respect.

But the other factor we need to look at which probably most people in the mainstream situation are familiar with is amyloid production. This is how it’s classically diagnosed, is looking for these plaques, amyloid plaques, on scan as defining Alzheimer’s disease from just normal aging, forget where you put the keys aging, versus Alzheimer’s Disease.

I heard a very good definition from a lecture one time, how you differentiate normal aging from Alzheimer’s disease. Normal aging is basically you forgot where you put the keys. That’s not Alzheimer’s disease. Alzheimer’s disease is you forgot what the keys are used for. That’s Alzheimer’s disease.

And amyloid production is also a big factor in that. There’s been some interesting research. Of course, we know that the amyloid is involved, probably not to the extent that many think. But what we do know, what we’re finding now is, well, the question needs to be answered, where did the amyloid come from in the first place. Is it the body just decide, “I’m gonna basically go into neurodegeneration”? No.

Research is now suggesting that, like every other illness we see, the allostatic load model, that basically what we see, the body, what it’s producing, whether it be high cholesterol or high blood pressure, it’s a response. Amyloid is now considered to be a response to disturbances in insulin metabolism and inflammation, and inflammation, of course, is most significant in terms of this discussion on gut microflora.

So the body, if you will, it’s kind of, I guess, for lack of a better term, like a scab, if you will. Like, we now know that the plaque in the coronary arteries is basically a scab. It’s basically a healing process generated to deal with various injurious agents. But if the response is too profound, the scab gets too big, and it gets too fragile, it can block blood flow, or it can crumble, if you will, like a fragile scab, and you get bleeding and forms a clot.

Same thing is happening in the brain with this amyloid, that this “healing response” can be so significant, because, like a scar or a scab, if you will, it’s nonfunctional tissue. So this healing response designed to fix something, unfortunately, it’s nonfunctional tissue, and if you get too much of it, now we lose brain function. So we do know that the gut microflora in the process of creating inflammation is going to upregulate the inflammatory cells, and the brain needs microglia, and we’re gonna get more amyloid produced.

And the same thing, the gut microflora upregulating inflammatory mediators will cause more insulin resistance, and this will cause more amyloid. But there’s one other area that’s interesting that I really wasn’t aware of until I started looking at the research, is that gut microflora can actually produce amyloid. Isn’t that interesting?

Dr. Hedberg: Mm-hmm.

Dr. Moss: And this can go through the leaky gut into the brain and actually contribute to what we see in the brain in terms of amyloid. So this idea which I think is revolutionary and important is that some of the amyloid in these scans came from sources outside the nervous system, very interesting.

Dr. Hedberg: One of the frustrating things about all this is that we know that these connections exist, but conventional medicine doesn’t really have that many tools in their box for correcting these gut issues, other than antibiotics or a few probiotics. So why don’t we shift and talk about some of the things we can actually do to improve gut health, improve the microflora? So can you talk about some dietary strategies and supplements?

Dr. Moss: Yeah, first of all, nothing new here about diet. It’s the usual things. It’s the whole foods diet. I found a particularly interesting paper that talked about how to reduce gut microflora amyloid production, and it’s going to be the usual things, whole grains, fresh fruits and vegetables, the typical Mediterranean diet, omega-3 fatty acids, no junk food, so nothing new there.

In terms of supplements, again, nothing new here. Green tea has been used. Different types of polyphenolic compounds have been used or demonstrated to reduce amyloid, so really nothing new there. Some of the herbals that have been looked at, no surprise here, turmeric, curcumin, no surprise there. Ginseng, Rosemary has been demonstrated, ginger, things that are really standard in the functional medicine, alternative medicine type of practice.

So basically another demonstration that really the idea of segmenting the body in terms of diseases and certain treatments is really a very artificial approach. So you wanna fix the brain, you just do what you do for the rest of the body is the real message here in terms of diet and supplements.

Dr. Hedberg: Right, and, for practitioners listening, in order to really figure these things out, make sure you’re getting a really good history going all the way back to birth, and what the patient’s health was like as an infant and as a child, antibiotic history, diet history, and all those kinds of things. And then a good stool analysis and possibly a SIBO breath test are some good ways to identify some of these microflora issues. Let’s go a little bit more into detail about the impact of probiotics on Alzheimer’s and some of the things that we’ve talked about.

Dr. Moss: Sure, of course, probiotics is one of the biggest controversies in terms of do they work, what microflora, what probiotics do you give. And so there’s a lot of controversy here. Of course, the whole discussion logically would suggest that if we have a dysbiotic situation theoretically probiotics should work, and I’ll talk about research on that in just a second.

But, Nik, you know better than anybody that just giving a probiotic to someone who has significant dysfunction, it’s just not that simple. And certainly, as you mentioned, assessment is crucial. I think these days what we’re beginning to understand in terms of the microflora impact systemically is that I tend to look at it in kind of three different types of disturbances.

Number one, we can just have an imbalance of resident microflora, too many of the ones that are in use in small amounts and too little of the ones that are normally supposed to be there. The classic example, of course, is candida. Candida is supposed to be there, but you get an overgrowth. That’s one issue that needs to be looked at.

Number two, is it growing in the wrong place? We’re supposed to have a little bit in your small intestine. Do you have too much? You know, the SIBO scenario which we are seeing more and more now due to various scenarios. And then, of course, the classic, I don’t like the word, but “parasites.” Are you getting an overt pathogen that may have occurred recently? And that’s easy usually to pick up in history, and it’s easy to find out if your patient developed a problem and they say, “Well, I went to India two months ago and drank the water.” Now, the Ganges, that’s easy.

What fools us in terms of pathogens is that these are very smart little organisms, and many times the exposure may have occurred decades ago. They went to India. They’re 60 years old. Now, they went to India when they were in their 20s, and there’s a pathogen that has been lying dormant but slowly creating inflammatory mediators, slowly creating metabolic disturbances, and slowly creating neurologic disturbances.

And so when we look at the idea of giving a probiotic, first of all, we have to have, as you suggested, some idea of what we are dealing with from a baseline perspective. Stool analysis comes into play, very often SIBO testing, a very good history, and, again, going all the way back.

I agree with you. Very often the mistake we make, we don’t go far enough back, particularly in terms of the pathogens. They can sit there for years in their dormant state just waiting, just waiting until the environment is conducive to their growth. But even when they’re waiting, they can still produce inflammatory mediators, which over the years can contribute to a problem.

So probiotics, I think, are going to be most effective when used as part of an overall treatment plan. Does the patient need some sort of antimicrobial therapy due to a SIBO scenario, a pathogen, or overgrowth of a resident organism? Do we need lifestyle modifications? Are there other dietary issues? But, with that in mind, when that’s done, yes, probiotics do work.

There was a specific study that I was able to find, and this was done on elderly patients. They were all diagnosed with Alzheimer’s disease. They were between 60 and 95 years. And the intervention they gave was a probiotic milk, contained four organisms, three lactobacillus organisms and a bifido organism. They assessed by use of what is known as the MMSE, mini-mental state examination, and after this intervention, they did find positive results.

So now what do we know about the other aspects? Baseline was not mentioned in the study. And, of course, not every patient responded well, but enough responded to get a significant finding. So probiotics, I think, have their place from a clinical standpoint when we’re looking at numbers of patients, and if we just give a probiotic, it’s gonna be very hit or miss. On the other hand, doing this type of comprehensive approach, I think we can get some very good results.

Dr. Hedberg: And a few additional assessment things to look at would be blood work. You talked a little bit about insulin resistance and inflammation. So I usually look at fasting glucose, hemoglobin A1c, fructosamine, and fasting insulin, and then also looking at markers of inflammation, like C-reactive protein, either quantitative or cardiac highly sensitive, fibrinogen, homocysteine, and erythrocyte sedimentation rate. Those can give us some kind of indirect clues as to something that could be going on in the GI tract, as well as CBC, complete blood count. So you can pick up a lot from there, but, as you said, direct testing with a stool analysis or something like that is gonna be our best approach.

And I’ve seen many insulin-resistant patients not really turn around until we’ve, so to speak, fixed their gut, and I think that ties into a lot of what you talked about today. And that was kind of the sticking point, because, as you know, the microflora is so intimately involved in glucose metabolism and the rate of absorption, as well as the inflammatory component. And, as you said, the more inflamed you are, the more insulin-resistant you can be and vice versa.

Dr. Moss: Yeah, I would agree 100%. I think all of us now in clinical nutrition and functional medicine are really beginning to appreciate that virtually all chronic illness there’s going to be an inflammatory component. It’s no longer if. It’s basically a matter of degree. It’s going to be there. And I think we know, we’ve heard for years, and years, and years treat the gut, treat the gut, but I think very often we have talked about treating the gut when there is gut symptomatology.

I think we have to really expand our thinking beyond just, “Well, I only treat the gut if they’re symptomatic,” to the idea if they have a chronic illness and through the method you mentioned finding inflammation, we really have to take a look at the gut and the gut microflora. Now, I’m not saying it’s 100% that it’s gonna be significant after we have to do some type of intervention on the gut, but I would say assume it until proven otherwise.

Dr. Hedberg: And that low-grade pathogen potential that you were talking about increasing inflammation, and potentially stressing the system, and then creating glucocorticoid resistance due to HPA axis dysfunction, and then creating more inflammation due to that resistance. I mean, we could talk all day about all these different connections to the endocrine system, and the nervous system, and the brain, and the rest of the body, but this was a great overview and very enlightening, very interesting connections there, especially to know that the beta-amyloid plaque can be produced by bacteria in the gut and then actually get into the brain and connect with Alzheimer’s. So fascinating information and I’m gonna be following this particular aspect of functional medicine very closely for a long time as we learn more. So thanks for coming on, Jeff. Really appreciate it. This was a great topic, and I’m sure it’s gonna be very useful to a lot of people.

Dr. Moss: Well, thank you so much, and I appreciate you having me on your show.

Dr. Hedberg: All right, well, thanks for tuning in, everyone. If you go to drhedberg.com, I will have all the show notes and links to anything we talked about today. And until next time, this is Dr. Hedberg. Take care, everyone.

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