The True Probiotic Superstar

Research on the intestinal microbiome is uncovering potential new probiotic species that could revolutionize medicine. The research is also destroying some rather long-held, but limited views on how to influence the composition of the microbiome. The focus in the marketplace has been on attempt to influence the microbiome through supplementation with lactic acid producing bacteria such as Lactobacillus and Bifidobacteria species. The truth is that while these organisms are important they play a rather small and limited role on the microbiome.

Through newer methods of identification of bacterial species in the microbiome coupled with a growing understanding of these organisms, they are other bacterial species that are showing much greater roles in impacting health and disease. There is one bacteria in particular that is exciting as it plays a key role in the health of the gut lining as well as it promotes improved insulin action to help fight obesity and diabetes. In fact, it turns out that the effects are not limited to its live probiotic effects, but rather to some of the compounds that it manufactures as it has been shown to be effective when it is either a live or heat-killed organism. It is not alone, several lactic acid producing probiotic organisms have also been shown to be effective when heat-killed. So, this commercial focus on live colony forming units maybe overstated. More on this later.

What is the Microbiome?

The gut microbiome refers to the complex and diverse system is composed of the genetic material from trillions of microorganisms (microbiota). Without question, the microbiome is a huge contributor to our health and wellness. Research shows that the microbiome has a profound impact on a variety of systems and plays crucial roles in digestive, immune and mental health. An imbalance in the intestinal microbiome may lead to a wide range of issues, ranging from occasional symptoms of digestive distress like gas and bloating, to broader systemic challenges such as obesity, diabetes, Alzheimer’s disease, inflammation, etc.

Meet Akkermansia Muciniphila

The best example of an important gut bacteria that not many people have ever heard of is Akkermansia muciniphila. It is not commercially available as a probiotic, but there are ways in which a person can increase their own supply of A. muciniphila through diet and supplementation. First, let’s take a look at A. muciniphila and why it is so exciting.

I have written about A. muciniphila before. It plays a critical role in the health of the mucin layer that protects the intestinal lining and maintains proper structure of the intestinal lining. That is why it is given its strain name muciniphila – the Latin suffix phila means love. So, muciniphila literally translates as “love of mucin.” A. muciniphila works with the cells that line the intestines to produce the mucin that goes a long way in protecting the gut lining from damage. Not surprisingly, higher levels of Akkermansia muciniphila are associated with improved intestinal barrier function, reduced intestinal permeability (leaky gut), and improved overall digestive and absorptive function.

All of the effects on the mucin layer by A. muciniphila are exciting, but what is really making researchers (and drug companies) excited are its effects on diabetes and obesity. As the levels of A. muciniphila goes down in the human microbiome, the rates of obesity, diabetes, inflammation, and metabolic disorders goes up. And, as the levels of A. muciniphila goes up in the human microbiome, the rates of obesity, diabetes, inflammation, and metabolic disorders go down. The assumption is that these disorders are associated with altered gut barrier function due to reduced mucin protection, which leads to the absorption of many gut-derived toxins that trigger a cascade of different systems that promote chronic inflammation and insulin resistance.

New Data:

Animal studies have shown A. muciniphila to prevent diet-induced weight gain and there is now human evidence to support the same effect. In the July 1, 2019 online edition of the prestigious journal Nature Medicine, a pilot randomized trial of A muciniphila administration among individuals with metabolic syndrome and insulin resistance showed quite convincingly that A. muciniphila holds much promise in perhaps tiding the now worldwide epidemic of obesity and type 2 diabetes.

Thirty-two subjects with pre-diabetes and evidence of the metabolic syndrome (abdominal obesity, elevated blood lipids, high blood pressure, etc.) were randomized to getting either a placebo, or live or heat-killed A. muciniphila. The active treatment groups taking A. muciniphila took around 10 billion bacteria (either dead or alive) daily for 3 months. The primary purpose of the study was to evaluate safety. A muciniphila passed that test with flying colors. It also displayed effects noted on multiple markers of metabolism and overall health. Compared with placebo, insulin sensitivity increased while total cholesterol and some markers of inflammation and liver function improved. There was also a significant decrease in the white blood cell (WBC) count in those who got the bacteria. The thought is the strengthening of the gut barrier led to a reduced absorption of gut-derived toxins that could trigger an increase in white blood cell levels.

Here is the interesting part that may be disruptive to many readers of the study – the heat-killed or dead bacteria outperformed the live bacteria. I have been stressing this effect for certain probiotics for years, but mainly to deaf ears. The marketplace is consumed with colony forming units over clinical data. That is a mistake in helping consumers get real results with probiotics and compounds designed to impact the gut microbiome.

Live vs. Heat-Killed Probiotics

One of the first approved “probiotic” drugs on the market for over 30 years and now in over 60 countries is strain of Lactobacillus acidophilus used in the treatment of diarrhea and gastritis. The bacteria in the product is heat-killed and also includes the culture medium. Here is the interesting thing about the development of this product, studies showed that the live bacteria, the heat killed bacteria, and even the cell-free culture medium were all effective. The cell-free culture medium refers to the nutritive solution that the bacteria were nourished in. How is this possible?

Well, it turns out the key mechanism of action is not the ability of the live bacteria to adhere to intestinal cells, but rather the presence of compounds produced by the bacteria that act against diarrhea causing organisms as well as exert direct effects on the intestinal cells to resolve diarrhea.

My purpose of explaining this mechanism of action of this strain of Lactobacillus acidophilus is to help pave the way in understanding what is going on here with A. muciniphia. One of the key features of this bacteria is that it is very “slimy.” A. muciniphila is covered in molecules known as exopolysaccharides that prevents white blood cells from breaking down a beneficial protein known as Amuc_1100 that is found in the membrane of A. muciniphila. It turns out that this protein appears to be the secret to the bacteria’s beneficial effects.

When purified Amuc_1100 is given to mice it exerts the same effects as the live or heat-killed bacteria. The reason why the heat-killed produces better effects than the live form of A. muciniphila is that it removes the exopolysaccharides coating, but leaves the Amuc_1100 intact.

Enhancing the Growth of A. muciniphila in the Human Microbiome

muciniphila is not expected to be commercially available as a probiotic until 2021, but I don’t think that is a big deal. As I have written in the past, we are becoming obsessed with the microorganisms and not focusing enough on creating the right intestinal environment to grow our own microbiome version of the Garden of Eden. Focusing on creating the right “soil” to grow A. muciniphila and other beneficial probiotics is in my opinion a more rational approach to establishing the optimum microbiome.

There are a few things that have been shown to be effective in promoting the growth of A. muciniphila, most notably a FODMAP diet, prebiotics, fish oils, and berberine:

FODMAP Diet

FODMAPs is an acronym for:

Fermentable – foods that are quicken broken down (fermented) by bacteria in the large intestine
Oligosaccharides – “oligo” means “few” and “saccharide” means sugar. These molecules are made up of individual sugars joined together in a chain. Beans are a common source of oligosaccharides.
Disaccharides – “di” means two sugar, so a disaccharide is composed of two sugar molecules bonded together. Sucrose is a disaccharide.
Monosaccharides – “mono” means single, so a monosaccharide is a single sugar molecule. Fructose is a monosaccharide.
And Polyols – these are sugar alcohols often used as sweeteners. Some examples are xylitol, maltitol, and erythritol

Clearly, not all FODMAPs are health promoting. Here is a list of some common foods and ingredients that are high in health promoting FODMAPs:

Vegetables: artichokes, asparagus, broccoli, beetroot, brussels sprouts, cabbage, cauliflower, garlic, fennel, leaks, mushrooms, okra, onions, peas, shallots.
Fruit: apples, apricots, blackberries, boysenberries, cherries, dates, figs, pears, peaches, watermelon.
Legumes: beans, chickpeas, lentils, red kidney beans, baked beans, soybeans.
Non-gluten grains: oats, amaranth, buckwheat, rice (brown, white, wild), millet, quinoa, and sorghum

Prebiotics

Prebiotic fermentable dietary fibers such as inulin, various oligosaccharides (fructo-, malto-, and xylo-), pectin, tapioca fiber, acacia gum and resistant starch. I recommend taking a total of 3 to 5 grams daily of one or more of these fibers.

Fish Oils

The omega-3 fatty acids in fish oils exert profound effects on the microbiome including an ability to increase levels of A. muciniphila. Fish oils providing higher levels of DHA to EPA exerts a more profound effect on the microbiome and greater anti-inflammatory effects, especially in the gut. The ideal ratio appears to be DHA 4: EPA 2: DPA 1. Interestingly, this ratio is very close to what is seen in wild salmon species. I recommend a minimum of 600 mg of omega-3 fatty acids daily.

Berberine

Berberine is an alkaloid found in many plants, but most notably in goldenseal (Hydrastis canadensis) and barberry (Berberis vulgaris). Berberine exerts significant beneficial effects on digestive health and the microbiome including increasing the levels of A. muciniphila. This effects partially explains its positive results in clinical trials in improving blood sugar control in type 2 diabetes, lowering blood lipid levels better than statins, and improving liver function. Take 500 mg two to three times daily if you are dealing with any of these metabolic disorders.

Final Comments

Microbial diversity is a key goal for the health of the microbiome. So, how do we achieve that goal? What is well-established in the scientific literature is that dietary diversity and an adequate intake of omega-3 fatty acids are the biggest determinant for diversity within the microbiome. Therefore, eat a diverse diet rich in those foods and compounds known to be associated with health. One of the beneficial features of most healthy diets, like the Mediterranean diet, is that they are a rich source of compounds that appear to promote the growth of A. muciniphila. What concerns me is that popular diets like the ketogenic diet and paleo diet are often very low in foods that promote this important organism. That could be a problem for some. So, if you are going to go keto- or paleo, be sure to focus on some foods or supplements that promote A. muciniphila.

Z

Reference:

Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 July 1. [Epub ahead of print]