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Primer(tm) -- Part 1

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Par Deus

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Primer™
Microbiomic Superfuel™

Bacteria need to eat, too. Pamper them. A well fed microbiome is a happy and healthy microbiome. Give them the gourmet shit. Primer is a generously portioned blend of 11 prebiotic dishes and desserts meticulously chosen to entice the good bacterial denizens and citizens of your gut to feed and breed, prodigiously, while starving and poisoning unwelcome pathogenic bacterial inhabitants. Grow your own, right at home.

Currently, probiotics are mostly thought of and used in relation to a healthy digestive system (reducing upset stomach, gas and bloating, diarrhea, and IBS type symptoms) and the immune system (coughs, colds, and general sinus and respiratory health). While they certainly are indeed useful for such applications, the ramifications of an unhealthy gut and microbiota go far, far beyond that.

The gut and its microbiome are essentially a massive endocrine organ, controlling and influencing basically your entire body and brain. And, given that all of the trillions of bacteria that call it home originally came from outside your body – and entered without your permission – it is by far the most important organ in which we can take steps to manipulate and take back control.

We will first look at some basic science and data on how this all works. Then, we will look at studies that have shown alterations in the microbiotic make-up of the gut, and the correlations they display in health and disease, suboptimal and optimal fitness, and just general things that everyone would consider part of good or bad life outcomes.

It is a massive subject, far too much to discuss in complete depth, here, so we’ll do our best to keep it as short and sweet as possible while still giving you enough background in this field to understand the shocking reality, scope, and importance of this microscopic invasion.

Subsequently, we will get down to business and specifically get into the science of Shock Treatment™, the first step in the process of making yourself king or queen of your own castle, again. We’ll show you how it can immediately ameliorate symptoms, while preparing the gut for a permanent fix, with special emphasis on a lean, healthy body.

Deus Vult!

 

The Basics

It basically works like this. The Western lifestyle, including diet, lack of exercise, and alcohol use (and, in all likelihood, genetics, though the data just isn’t there, yet) leads to an imbalance of the bacterial composition of the gut (1,2). This results in the excess production and release of inflammatory signals, such as Lipopolysaccharide, TNF-alpha, interleukins, and prostaglandins, which subsequently escape the gut and enter the rest of your body (3).

Though, they all contribute to the pathologies we will cover in various ways, it is Lipopolysaccharide (LPS) that we will focus on the most. Within the gut, this leads to the general digestive issues and inflammatory bowel syndromes like IBS and colitis that you have commonly known probiotics as being used to alleviate (4).

While fixing digestive disorders will come along for the ride, our primary focus is going to be on body composition and metabolic health. In other words, we want to make you leaner, protect against diabetes, and help keep you from having a heart attack or stroke. However, there really is so much more to it than that, as a few quotes from the literature aptly demonstrate:


“Changes in the composition of the gut microbiota (dysbiosis) may be associated with several clinical conditions, including obesity and metabolic diseases, autoimmune diseases and allergy, acute and chronic intestinal inflammation, irritable bowel syndrome (IBS)…” (5)

 

“In this milieu… disturbance of the gut microbiota balance and the intestinal barrier permeability is a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.” (6)

 

“Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome… Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.” (7)

 

As you can see, alterations in the microbiota can affect basically everything, but that there is also hope for change.

Getting back to the gut and body composition, the aforementioned Lipopolysaccharide (LPS) leads to overactivation of cannabinoid receptor 1 (CB1) within the gut, which causes an increase in intestinal motility (speed of food going through) in the proximal parts of the intestine. This leads to less absorption of nutrient feedback signals that tell the brain you are well fed, and that it is time to stop eating (8). Concurrent with this is an increase in transit time in the colon, which results in a greater total harvest of caloric energy from your food (9, 10).

In other words, the signal your brain is getting is that you are not getting enough food, while you are actually extracting more calories from what you eat. This not only directly leads to more fat accumulation from harvesting more calories, it lends itself to over-eating. This aggravates the cycle further, as overeating and increased adiposity are themselves inflammatory. So, what you have is more inflammation, more dysfunction, greater food intake, greater extraction of food, more fat accumulation, then REPEAT!

The carnage does not even end here. Along with this inflammatory state is a disruption in the intestinal barrier. Intestinal permeability is increased and these inflammatory agents spill out systemically. This is often called a “leaky gut”. This results in a low-level inflammatory state in the entire body. The biggest culprit here is, once again, LPS (11).

LPS activates CB1 receptors in the body and brain, just as in the intestine. In the fat tissue, this leads to activation of PPAR-gamma, and an upregulation of triglyceride synthesis, fat cell formation, and fat storage (12). In the brain, activation of CB1 increases orexegenic pathways, thus increasing appetite, hunger, and ultimately, food intake (13). This should not much as much of a surprise considering “the munchies” that accompany intake of famous cannabinoid receptor agonist, marijuana.

And, LPS is not done yet, not at all. It also activates Toll-like Receptor 4 which, along with other inflammatory signals (TNF-alpha, interleukins), promotes both insulin and leptin insensitivity, peripherally and centrally (14, 15).  At this point, your adipostat (the thermostat for your body fat level) is wrecked.  Your ability to control food intake is gone, and you are a fat storing machine. Obviously, this is not what you want your body doing to itself. It is not what you want it doing to you. It is not what you want it doing to your life.

Oh, and to top it off, atherosclerosis, heart disease, and stroke are promoted by these same inflammatory pathways. Combined with the increased body fat and insulin resistance, you officially have all of the perfect ingredients for the dreaded Metabolic Syndrome (16, 17).

And, it is just a bunch of microscopic bacteria that call your gut “home” causing all of this devastation.

 

General Data

The most well-known genera of bacteria in commercial probiotics are Lactobacillus and Bifidobacterium. They are also among the most common in the body, along with several other ones which are not commercially available, but which we can manipulate with supplementation.  We will talk about these in length in the SupraBiotic™ and Primer™ write-ups.

Unfortunately, Lactobacillus belong to the Firmicutes phylum which has been found to be associated with weight gain and obesity (18-20). Just a 20% increase in Firmicutes (which Lactobacillus is usually the primary genus) with an equal decrease in Bacteroides results in an increased energy harvest of 150 calories per day in humans (21). That is equal to 15lbs of fat per year!  The Western style diet promotes these negative changes in microbial proportions (22). Thus, one can plainly see why it can be so difficult to get lean, as well as how easily obesity has become an epidemic.

Interestingly, smoking cessation produces the same negative changes in bacterial composition, while gastric bypass surgery improves it (23-24). The well-known effects on weight with both of these further highlights the negative body compositional effects of this intestinal dysbiosis.

In addition, probiotic treatment with several Lactobacillus species that are in a great number of commercial formulations, including Lactobacillus acidophilus, Lactobacillus fermentum, and Lactobacillus ingluviei , have been directly associated with weight gain and obesity (25). Type-2 diabetics had significantly more Lactobacillus, with L. acidophilus being particularly bad in this regard (26).  Further, L. reuteria and L. sakei have been found to be positively associated with obesity and body mass index (27-29). They probably don’t tell you that on the label.

More powerful evidence of the profound effect of the microbiota on body weight and metabolism come from studies on “fecal transfer”.  And, yes, that is exactly what it sounds like – transferring poop from one subject’s intestine to another’s.

In twins, transfer of an obese microbiota to lean mice was accompanied by an increase in bodyweight, fat mass, and a dysbiotic alteration of the Firmicutes:Bacteroides ratio to reflect that of the obese model (30). A similar transfer replicated the obese phenotype with increased weight gain, lipogenesis, adipogenesis, overeating, and lower satiety, as well as inflammation and hyperglycemia in formerly lean, healthy subjects (31, 32).

On the other side of the coin, transferring the intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, as well as reversing obesity and gastrointestinal issues (33). It also reduced markers of metabolic syndrome, inflammation, and oxidative stress in animals challenged with high-fructose diets (34).

Obviously, while it highlights the science, doing a fecal transfer is not terribly practical, appetizing,  or readily available -- unless maybe you are in California.

Fortunately, there is good news. While several species and strains of lactobacillus have been found to promote weight gain, several have also been found to protect against it. And, of course, we only used the good ones. Furthermore, Bifidobacterium have shown only positive effects to a remarkable extent. 

Bifidobacterium are anti-obesity and lipid lowering, decreasing fat weight, blood glucose, cholesterol, and triglyceride levels (35). They are higher in lean subjects, as well as being lower in obese (36, 37). They are significantly lower in type-II diabetics and have been shown to improve glucose tolerance as well to decrease inflammatory signaling (38-40). In addition, they increase levels of EPA, DHA, and CLA in fat tissue and the brain (40). They have also been found to decrease with aging (41).

We can also readily manipulate levels of the good bacteria that are not commercially available such as Bacteroides species, Akkermansia Muciniphilia, Faecalbacterium Prausnitzii, and Roseburia via supplementation of ingredients that ARE available.

So, let’s get to it.

You may have noticed that almost no probiotic formulas contain just a single species of bacteria, nowadays. And, if you did not, I will just say that it is for a good reason. They work better in combination. This applies to the prebiotics that feed them as well. You need a variety of prebiotics to grow a variety of probiotic bacterial species.

First of all, microbial diversity seems to be good, in and of itself. Essentially, a diverse gut is a healthy gut (42). Obesity has been associated with a lack of microbial diversity and, as you might expect, lean subjects have greater microbial diversity in the gut (43-45). Insulin sensitivity is also improved along with diversity increases (46).  Finally, in the interesting but not terribly shocking category, exercise increases microbial diversity (47, 48).

Increased diversity also works to specifically create an environment where probiotic bacteria can thrive, thus enhancing their ultimate performance (49). Compared to individual strains alone, this diversity increases adhesion to intestinal mucus, which is necessary for most survival, growth, and activity (50, 51).  Conversely, bacteria inhibit adhesion of pathogenic bacteria better when in combination (52, 53).

However, you do not want to just try to have every single species and strain in existence growing inside of you. It needs to be done rationally. If not, they can interfere with each other’s actions and compete for space and resources (54-56). 

But, maybe the most interesting benefit of supporting a combination of bacteria is through cross-feeding. This is when one bacterial species produces metabolic substrates the other species and strains use for fuel (57, 58). Bifidobacterium adolescentis is the most interesting and important species in this regard as it functions as THE archetypal cross-feeder for several of the most important and impressive strains of bacteria. And, those strains are not commercially available. B. adolescentis produces acetate and oligosacharrides which are then consumed by these acetate utilizing, butyrate and propionate producing bacteria (59).

For references, see "View Full Science Write-Up" here: http://neobium.org/product-line/primer/

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