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Ask the Expert: Dr. Emeran Mayer on Butyrate, Akkermansia muciniphila, and More

Ask the Expert: Dr. Emeran Mayer on Butyrate, Akkermansia muciniphila, and More

In our new Ask the Expert series, we're sitting down with renowned science and medical professionals to get their insights into how to stay healthy.

In our third edition of Ask the Expert, Pendulum CEO and Co-Founder Colleen Cutcliffe chatted with Dr. Emeran Mayer, a Gastroenterologist, Neuroscientist and Distinguished Research Professor in the Departments of Medicine, Physiology and Psychiatry at the David Geffen School of Medicine at UCLA.

As one of the pioneers and leading researchers in the role of mind-brain-gut interactions in health and chronic disease, he has made major scientific contributions to the area of basic and translational enteric neurobiology with wide-ranging applications in clinical GI diseases and disorders.  


What are some specific nutrients vital for proper gut function? 

When we talk about gut health, a lot of people think about what goes on in the end of the small intestine and in the colon. That’s where a majority of our gut microbes live. The processes that are going on in these regions of the gut have turned out to be very crucial to many functions in our bodies. That's where the great majority of our gut microbes live. 

What’s important for the health of this part of our digestive tract are the nutrients targeted at the gut microbiota. When we eat a meal, a great majority of the macronutrients are rapidly absorbed in our small intestine, all the macronutrients are taken up and we don't really have to worry about this aspect well unless you have malabsorption. What we have to worry about is that fewer and fewer components or proportions of what we eat gets down to the microbiota and nurtures microbes.

The most important part of this are these microbiota accessible carbohydrates (MACs) also referred to as dietary fiber. These are all the molecules that are not absorbed in the small intestine that move down into the realm of the microbiome where they are being metabolized, many of them into short chain fatty acids, and play a major role in maintaining the health of that system.


What role does butyrate play in glucose control for people with type 2 diabetes? 

Butyrate is one of the short chain fatty acids. I like to refer to the short chain fatty acids as the main currency in the microbial world. Butyrate receptors are in a wide range of cells within the gut, ranging from epithelial, endocrine cells to immune and nerve cells.

Because of the ubiquitous expression of these short chain fatty acid receptors on various gut cells, butyrate has a wide range of homeostatic effects on gut function. We have so many different cell types that all interact with each other and interestingly short-chain fatty acids are a major influencer in maintaining proper functioning of this complex system.


How is butyrate involved in improving immunity and reducing inflammation? 

The gut associated immune system is a complex system. he gut microbes are separated from the immune system in the gut that's just really microns away from the inside of the gut lumen and that's accomplished by a mucus layer made up of un-absorbable carbohydrates produced by specialized gut cells. The quality and the thickness of this mucus layer is a major determinant of how many of these microbes get in direct contact with the gut associated immune cells.

If the mucus layer is compromised luminal microbes can get in direct contact with dendritic cells, which can initiate a whole cascade of immune activation which initially could be limited to the gut associated immune system, but typically what happens is this spreads throughout the body and this inflammation can affect many different organs and sound systems throughout the body including the pancreas, brain, liver and fat tissue. 

It comes down in a simplistic way to the integrity of this gut barrier. he most important part is the thickness and quality of the mucus layer which keeps our microbial world that lives inside of us away from the immune cells. If this gut barrier is compromised it’s often referred to as “leaky gut.”


Tell us about this new strain Akkermansia muciniphila and why everyone should know about it.

Akkermansia muciniphila and several of its strains have been implicated both in clinical studies as well as research studies to be a major regulator of the mucus layer that plays an integral part of the gut barrier function. 

The most important link Akkermansia muciniphila has to our gut health, gut microbial health and our metabolic health, is related to its role in optimizing the homeostasis of our gut mucus layer. That mucus layer essentially is the main barrier between the microbial universe inside of us, both the good and the bad microbes and the gut associated immune system.

The two are just microns away from each other so if anything goes wrong with the mucus layer, and this has now been shown in many studies, there is a direct contact between immune cells into the gut lumen and microbes interacting with these immune cells triggering a whole cascade of inflammation or immune activation in the gut and beyond. 

Akkermansia muciniphila strains have been shown to play a major role in the regulation of this mucus layer. There are different strains implicated in the stimulation of cells within the gut that produce the mucus, but also in the degradation of these molecules.

Akkermansia muciniphila strains can live off the complex carbohydrate molecules that are making up the mucus layer if you don’t feed them. Otherwise, they can live off the carbohydrates that are making up the mucus layer. They can also play a major role in stimulating production and integrity of this layer. 

There are other microbes that have been implicated in the role of the mucus layer but I think the greatest attention has been focused on Akkermansia muciniphila strains. 


What can people do to maintain a healthy gut microbiome? 

In my view, on top of the priorities list is clearly a healthy diet. There are many factors that converge on this important interface between the gut microbiome and our immune system. For example, there is influence of the autonomic nervous system that can influence that permeability in response to psychological stress and emotioonal states, but I think today the most important and the easiest thing that you can do is to pay attention to what the needs of your gut microbiota are and not so much on the needs that we as the hosts have.

The great majority of discussions about the right diet has been focused on how much protein, how much sugar, how much fat is good for you -  and that's all not that relevant for the gut microbes. What's relevant is these microbiota targeted components of food, such as fiber or microbiota accessible carbohydrates (MACs) and polyphenols.

There are still debates about different benefits of different diets like ketogenic, paleo and low carb. What I would say is most important is that a largely plant-based diet has the highest amount and the highest variation of these beneficial food components for the gut microbes. Importantly, the greater variety of fruits and vegetables the better for your gut microbes. 


What makes Pendulum Glucose Control different from every other probiotic out there?

There’s a vast number of probiotics out there that all claim to have various health benefits from general well-being to anti-inflammatory effects. 

There's been a lot of controversy recently about the health benefits of probiotics for specific GI disorders and the great majority of these probiotics that have been criticized contain generic probiotic strains, like lactobacillus and bifidobacteria, that have never really been designed for a particular health benefit. Therefore, I support that skepticism that has been expressed by the American Gastroenterological Association about the great majority of probiotics that are out on the market, but the product that Pendulum has developed clearly stands out in that respect.

The Pendulum product, Pendulum Glucose Control, which is a combination of five microbial strains including an Akkermansia strain together with a prebiotic, really stands aside quite distinctly from the great majority of other microbes. Pendulum Glucose Control has been specifically developed for a very important medical indication, namely glucose control, lowering of hemoglobin A1C and type 2 diabetes mellitus and that has been tested in animal models and confirmed in a recent randomized controlled clinical trial.


How do you differentiate good probiotics from bad probiotics?

That's a very difficult question. If you go on the internet or if you talk to people that promote probiotics, they usually say theirs is the best, that it has the greatest number of CFUs, or colony forming units, it has the largest number of microbial strains.

These are unvalidated measurements or indicators for the benefits of a probiotic. It’s never been evaluated that if you take one one strain as opposed to fifteen strains that the combination is more beneficial. I'm personally very skeptical of any of these claims that companies make about these probiotic products. The biggest problem with many of these products is that they don't have scientifically demonstrated health benefits in humans.

The criteria that I would use is solid, high quality, controlled, randomized clinical studies of a probiotic where patients taking the product have demonstrated a measurable, objective benefit.

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