Demystifying GLP-1, a probiotic species linked to living 100 years, and you are not alone.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays a central role in regulating blood glucose levels and energy balance. It is produced by specialized L-cells located in the lining of the distal small intestine and colon in response to nutrient ingestion. When released into the bloodstream, its aim is to maintain metabolic homeostasis. 

Primarily, GLP-1 enhances glucose-dependent insulin secretion from pancreatic beta-cells, which aids in lowering postprandial blood glucose levels. In parallel, it suppresses the secretion of glucagon from pancreatic alpha-cells, further contributing to the regulation of blood sugar. In short, through multiple pathways, it can help regulate blood sugar, in higher levels, quite substantially. 

Improved  blood sugar regulation and disposal of excess blood glucose truly is at the heart of improving one’s metabolism and thus, their ability to burn stored body fat with a greater propensity, as well as reducing risk of pretty much all disease. Additionally, GLP-1 slows gastric emptying, which helps moderate the rate of nutrient absorption and promotes a feeling of fullness. This satiety effect can lead to reduced food intake, thereby supporting weight management.

Beyond its immediate impact on glucose metabolism, GLP-1 has been implicated in cardiovascular protection and may exert beneficial effects on the brain, among others. Its multifaceted actions have made it a target for therapeutic agents in the pharmaceutical industry, including GLP-1 receptor agonists like Semaglutide aka “Ozempic™️” . 

Overall, GLP-1 is a critical hormone that links nutrient ingestion to essential metabolic responses, ensuring proper glycemic control and contributing to long-term health. It is because of this that we could all benefit from a better understanding of how to naturally harness the power of this hormone. 

In my next segment, I will actually discuss a keystone probiotic species that could be linked to greater GLP-1 production and secretion, but first, let’s learn a bit more about how the body produces GLP-1. 

How GLP-1 is Produced Inside the Body

Short chain fatty acids (SCFAs) are metabolic byproducts (also called “postbiotics”) produced by the gut microbiota during the fermentation of dietary fibers, and they play a key role in stimulating the production and release of GLP-1 from intestinal L-cells. Here’s how this process works:

✔️ Receptor Activation: SCFAs—primarily acetate, propionate, and butyrate—bind to specific G-protein coupled receptors (GPCRs) on the surface of L-cells. Activation of these receptors initiates intracellular signaling cascades that lead to an increase in intracellular calcium and cyclic AMP (cAMP), both of which are critical signals for hormone secretion.

✔️ Stimulation of GLP-1 Secretion: The receptor-mediated signaling ultimately triggers the excretion of GLP-1 from the L-cells into the bloodstream. The hormone then acts on various tissues to enhance insulin secretion, reduce glucagon release, slow gastric emptying, and promote satiety, contributing to improved blood glucose control and energy balance.

✔️ Influence on Gene Expression: In addition to stimulating immediate secretion, SCFAs—particularly butyrate—may also influence the expression of genes related to GLP-1 production. Butyrate is known to inhibit histone deacetylases (HDACs), which can lead to epigenetic modifications that enhance the transcription of the proglucagon gene, the precursor to GLP-1. This effect could help increase the overall capacity of L-cells to produce GLP-1 over time.

If that’s all a little too “scientific” sounding, in summary, postbiotic SCFAs not only serve as immediate signaling molecules that trigger GLP-1 release but may also promote its longer-term production through gene regulatory mechanisms.

Now, let’s reverse engineer this as we head into our next segment.

SCFAs not only stimulate the secretion of GLP-1 naturally, but also promote the long term health and production of this key hormone inside the intestines.
So, these “postbiotic” SCFAs are pretty darn important then.

And what produces these SCFAs?

Our beneficial gut bacteria, also known as “probiotics”. 

Naturally, it comes full circle back to the health of your gut microbiome.

A little known bacterial species that inhabits the gut, and lives in the mucus layer that covers the intestinal wall, is quickly gaining momentum as a potential key cog in improving healthspan and overall longevity.

It is called Akkermansia (ak-er-man-see-uh).

This bacteria is found in high amounts in the guts of the centenarian population of Sardinia which is considered one of the “blue zones”, or areas of the world where people or specific cultures have dramatically longer overall longevity and healthspan (living free of disease) than other parts of the world. 

So what in the world is this gut microbe, and why does its prevalence in the gut appear to be equated with a longer, healthier life, free of disease?

The Role of Akkermansia

Akkermansia is technically a genus of bacteria, so when I refer to Akkermansia in this segment, I am actually referring to the only species in its genus found in the human gut Akkermansia muciniphila.

Akkermansia specializes in degrading the mucus in the intestinal wall in which it lives, and uses it as its energy source. This function of degrading the mucus of the intestinal wall helps with mucus turnover, which happens to be critical for gut health. 

It plays a critical role in maintaining the integrity of the intestinal barrier (which helps prevent “leaky gut”), helps modulate immune responses, influences metabolic pathways, and appears to promote healthy aging, thus, making it a very promising probiotic as we continue to research and learn more about how we can improve and extend our longevity. 

Akkermansia is also considered a keystone species. A keystone species is an organism that plays a crucial role in its ecosystem. In this case, the gut microbiota. 

Furthermore, a keystone species is especially important for the stability of its ecosystem, and a lack of a keystone species can cause a dramatic shift in the health of the environment it inhabits. This is the case for Akkermansia in the gut. 

Akkermansia Produces Postbiotics

As Akkermansia consumes the mucin in the mucus layer, it releases byproducts known as postbiotics such as short chain fatty acids (BINGO!), sugars, amino acids, sulfate, and other molecules that can be used as energy sources for other gut microbes. 

As a result, higher levels of Akkermansia helps stimulate a balanced and healthy microbial environment in the gut, which is most likely why it’s known as a keystone species. 

Akkermansia and Mucus Turnover

The mucus layer plays an important role in maintaining the integrity of your intestinal barrier by protecting it from harmful microbes and pathogens. However, to keep its defenses up, your mucus layer must be continually turned over and refreshed. Because Akkermansia consumes mucins found inside the mucus layer as its energy source, it causes the mucus layer to degrade, which then forces it to turn over and refresh, thus helping to maintain the integrity of the intestinal barrier. 

Akkermansia and Metabolic Dysfunction

Metabolic dysfunction in the body has been shown to lower your metabolism, increase your risk of diabetes, heart disease, liver disease, and cancer as we discussed last week. Akkermansia and its positive effects on overall metabolic function have been pretty well studied. 

As mentioned above, short chain fatty acids are a byproduct of Akkermansia feeding on mucins, and these short chain fatty acids play an important role in metabolism by serving as energy sources for other microbes and helping to regulate gene expression. These short chain fatty acids can also be transported to other parts of the body where they can be used as energy metabolism substrates in other tissue. 

And again, it is these short chain fatty acids (postbiotics) that are used to produce healthy and higher levels of GLP-1 in the intestines. 

In short, Akkermansia produces short chain fatty acids that assist in energy metabolism in the body, and anytime the body is more effective at energy metabolism, the better it is at burning calories and regulating blood sugar. 

Eating to Increase Akkermansia Populations

Polyphenols are antioxidants found in foods that act as prebiotics for many probiotics, including Akkermansia.

Therefore, eating polyphenol rich foods will help to increase your numbers of Akkermansia in the gut and intestines. 

Olive oil is an oil that is very rich in polyphenols, and has many other therapeutic properties that have been shown to increase longevity and decrease risk of age related diseases. I personally take a big swig of olive oil every single night, as growing research continually points to olive oil being one of the most disease preventive, healthspan inducing foods on the planet. 

Don’t sleep on dark chocolate either. A high quality organic dark chocolate is loaded with polyphenols, and in all honesty, is right up there with olive oil as one of the best anti-aging foods on the planet. 

Green tea and coffee are both rich in polyphenols. The rub is with coffee that much of the beneficial antioxidants are found in the oils, which do oxidize once the beans are ground, so anytime you can grind your beans fresh, as we do when we brew a cup of coffee or espresso at NONA, you will be drinking much more bioactive polyphenols. 

Dark red fruits and berries are also rich in polyphenols such as pomegranate, goji berries, strawberries and raspberries. 

Dark berries also contain high amounts of polyphenols, such as blackberries, wild blueberries, and açaí, which contains 3x the antioxidants of blueberries.

Finally, don’t forget about red wine. Red wine is rich in polyphenols, and is one of the reasons red wine is widely considered one of the most effective anti-aging foods, and even cancer preventive foods on the planet. If you haven’t, be sure to check out my blog on choosing an ‘old world style’ wine for the healthiest glass of wine.

Sometimes it’s good to just know that you are not alone.

In continuing with our new year’s theme of quotes and anecdotes from Matthew McConaughey’s “Greenlights”, I have an anecdote for you. 

Matthew, in the midst of what felt like an existential crisis in dealing with this newfound, and seemingly overnight fame, set out to hit the open road.

He had read about a monastery in the southwestern part of the country that would take you in if you were able to find them. 

There he mentioned to one of the monks that he was dealing with some internal strife and asked if there was anyone he could speak to about it. 

“Ahh! Brother Christian”, was the recommendation. 

Matthew and Brother Christian went for a walk in the desert and Matthew began pouring his heart out to him, on and on, for hours. 

Brother Christian never said a word, and just listened to Matthew the entire time. 

Finally, when Matthew had run out of gas, and had gotten everything off his chest, Brother Christian seemed to think for a moment, leaned in, and whispered:

“Me too.”

The human condition is just that…the HUMAN condition. 

It’s not the Seth condition, the Mary condition, or so on.

Our problems may differ from person to person, but in the end, we all deal with the same fears and anxieties. 

As we’re all engaged in this overall beautiful experience that is the human condition, that yes, does come with its strife, its misfortune, anxieties, and issues; sometimes the most cathartic thing is to know that you and we, are not alone.