Leaky Gut: Recipe for Chronic Illness?

About 15 years ago, it was discovered that most chronic illnesses were associated with something called chronic low grade inflammation. Chronic elevation of certain inflammatory markers such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and Interferon gamma (IFNγ) seemed to be associated with the vast majority of diseases that we deal with from metabolic syndrome (diabetes, obesity, heart disease), cancers & autoimmune conditions.

The big question was what is the source of this chronic low grade inflammation? In the last seven years or so, that question has been answered by big mainstream research institutes such as the NIH, American Diabetic Association & The American Heart Association, which have published dozens of papers showing that chronic presence of LPS is the biggest source of chronic low grade inflammation, which then becomes the foundation for chronic disease. And it all starts with a dysbiotic microbiome.

Leaky Gut: Foundation of Chronic Illness

Leaky gut is the more common or colloquial term for metabolic endotoxemia: metabolic refers to the process of digestion, and ‘-emia’ means it's associated with blood, so metabolic endotoxemia means an endotoxin is now present in your blood at measurable levels. After a meal, typically within 3-5 hours, you can see the increasing levels of endotoxin within your blood which confirms whether metabolic endotoxemia, or leaky gut, is present. To define it as leaky gut, a minimum 5-fold increase of circulating endotoxin 3-5 hours after the meal must be present. A typical person might get a 1-2x increase of endotoxin & can deal with it pretty well, but once you start getting a 5-6x increase in endotoxin circulation level after every meal, it becomes really hard to for the body to recover from. This sets the stage for chronic low-grade inflammation, the foundation of chronic illness.

LPS: The Endotoxin in Leaky Gut 

Lipopolysaccharide (LPS) is the endotoxin in metabolic endotoxemia, or leaky gut. LPS is a constituent of the cell membrane structure of gram negative bacteria present in our bodies; bacteria use it for numerous things like cell signaling. It's perfectly fine when LPS is in the cell membrane of the bacteria; it becomes a problem when those cells break open and LPS is released. If the intestinal cells are leaky, meaning there are gaps between them, then LPS is allowed to enter circulation causing a massive issue. To recap, having LPS in the gut microbiome is perfectly normal; it becomes abnormal when the barrier of your intestinal lining is compromised & LPS is allowed to leak through constantly. 

What happens when LPS leaks through into circulation? Your immune system is designed to detect LPS because it uses that as a marker for the presence of infective bacteria. Over millions of years, your immune system has come to recognize that if you have a high level of LPS in your blood, it signals a blood infection and it takes it very seriously. This elicits a massive systemic inflammatory response because your immune system views elevated levels of LPS as potential blood poisoning (or septicemia). If your gut is leaky, every time you eat food your body is going through a mini blood-poisoning in the 3-5 hour period after that meal, and the immune response can remain for up to two weeks from a single meal. That's how profound that immune response is.  

You'll find LPS as a culprit within all areas of the body:

  • In lung disease, people who have chronic obstructive lung disease or who are highly susceptible to pneumonia tend to have more LPS in the lung microbiota
  • In the brain, LPS can interfere with dopamine & serotonin binding and the ability of your receptors to bind hormones
  • In the skin, accumulation of LPS creates inflammation in the sebaceous glands which can lead to acne & other inflammatory skin conditions 
  • In joint issues such as rheumatoid arthritis, you'll see an accumulation of LPS in those joints which triggers an inflammatory response
  • In diabetes, there's something called central insulin resistance, which happens when LPS gets accumulated in the hypothalamus region of the brain & interferes with the brain’s ability to read blood sugar levels. This is a major driver of the massive proliferation of Type 2 diabetes that's occurring in the world
  • In neurodegenerative disorders such as Parkinson's and Alzheimer's. At the onset, both conditions are triggered by the accumulation of LPS in the brain & the central nervous system respectively. In both cases, inflammatory responses are triggered which begins neuro degeneration and the progression to those diseases. 

Restoring Balance: Fixing Our Inner Ecology 

Now that we’ve established how profound & pervasive LPS is and the significant role it plays in virtually every chronic disease that affects us, let's shift our focus on how we can reduce the amount of LPS that's leaking into the circulatory system on a daily basis. The good news is you can absolutely reduce, eliminate & repair the problem because it all comes down to an ecological issue within the microbiota, which you can fix through a number of behaviors. This is true at any age so it's never too late to make improvements. 

The 2 key features of a healthy microbiome which protect it against metabolic endotoxemia, or leaky gut, are:

1) Microbial Diversity 

2) Increase in Keystone Species


The first feature of a healthy microbiome is microbial diversity; the more diverse your gut microbiome is, the healthier you are. In fact, studies show that diversity in your microbiome actually dictates longevity and is inversely correlated with chronic illness, infection, etc. 

Six ways of increasing microbial diversity are:

  • Diversity in your diet
  • Periods of fasting 
  • Getting outside 
  • Reducing exposure to herbicides
  • Cleaning up your personal care routine 
  • Not over-sterilizing your home 

The first & one of the key ways of increasing the diversity within your microbiome is to increase the diversity with diet; the more different types of foods you consume, the more diverse your microbiome is. Some anthropological studies estimate that our ancestors consumed upwards of 600 different types of foods annually, whereas today the average person eats only about 15-6 different foods. 

Second, which is counterintuitive, is not feeding the microbiome (i.e. fasting), which can dramatically increase diversity within the microbiome. The microbes within your microbiome are layered into different types of fermenters: primary, secondary & tertiary, that do their jobs during different parts of the metabolic cycle. For example,  when you eat, the primary fermenters are going to digest the food & produce secondary metabolites for the secondary fermenters, who are then going to feed another layer of microbes, and so on. This whole cascade where microbes feed each other is called cross-feeding within the microbiome, and it could take 10 hours before the third layer of microbes are actually getting what they need. If we’re constantly adding food into the system, then it selects for the primary fermenters and the microbes at the base hardly get to activate their metabolic activity, which means they don't get much representation & time to multiply. So a period of fasting to allow this cascade of microbes to go through their metabolic processes can be very important. 

The third way of increasing diversity is by getting outside. It is pretty clear in the research that more contact with the natural environment can dramatically increase the diversity in your microbiome because you'll pick up organisms that will actually stimulate the growth of some of the endogenous species within your microbiome. Fourth, reducing exposure to things that are hurting your microbiome. When it comes to food, try to go organic as much as you can so you get less exposure to pesticides and herbicides which are known to be like antibiotics in your gut & bring down diversity. A study at King's College showed that as little as three weeks of exposure to environmentally ‘safe’ levels of Roundup (a herbicide) reduced microbial diversity quite dramatically. 

The fifth change that you can make would be looking at your personal care products; lotions, soaps & shampoos. All those things contain chemicals which will have a negative impact on your microbiome so if you can clean up just one of your personal care products it's going to have a huge impact. Finally, your home environment, which does not need to be sterile. There's a long term Finnish allergy study which showed that homes that use more sterilization had kids with higher incidence of allergies, viral infections, microbiome dysfunctions, etc. So trying to keep your home environment less sterile is actually good. 


The second key feature of a healthy microbiome is the presence of Keystone strains or species. These are organisms within the microbiota that not only protect you through a lot of metabolic functions but also support & protect the rest of the microbiome. Like a keystone in the arch of architectural design, they maintain the structure of your microbiome. 

Some of these keystone species are Faecalibacterium prausnitzii, Akkermansia Muciniphila & Bifidobacterium Longum. Lots of studies show they are inversely correlated with disease. For example, high levels of Akkermansia Muciniphila  protect against the 60 conditions or so under metabolic syndrome. With Faecalibacterium prausnitzii, high levels protect you against all kinds of inflammatory bowel conditions such as IBS, Crohn's, colitis, colorectal cancer, and so on. These are really important species within the gut but since they’re anaerobic (don’t like oxygen), you're not going to find them in probiotics.

Some of the ways you can increase keystone species include:

  • Increasing polyphenols in diet
  • Fasting
  • Resistant Starches & Complex Fibers
  • Precision Prebiotics & Spore-Based Probiotics 

Akkermansia Muciniphila loves polyphenols so if your diet is rich in polyphenols, you're doing a great job. The good news is there are some really fun polyphenols like dark chocolate, red wine, and colored fruits & vegetables. Akkermansia also loves fasting. For Faecalibacterium prausnitzii & Bifidobacterium Longum, certain types of resistant starches & complex fibers like oligosaccharides will feed these species. To make all of that easy, Microbiome Labs created a product called MegaPre, which is formulated with these unique oligosaccharide or prebiotics that have been clinically shown to specifically feed these important keystone strains. A study showed that in a 3-week period, just 1 scoop a day resulted in a 100-fold increase in keystone species. 

Another way of increasing keystone species and sealing the gut is with spore- based probiotics. In a 30 day study in individuals that had severe leaky gut or metabolic endotoxemia, taking megaspore alone without any other interventions resulted in a 60% reduction in the amount of LPS leaking into circulation every day.  Along with that massive reduction in LPS, key inflammatory cytokines were reduced quite dramatically. While Megaspore reduces metabolic endotoxemia quite dramatically, MegaPre increases the growth of the keystone species. Add in some of the lifestyle changes mentioned and you'll have a profoundly different gut microbiome that’s protected against LPS endotoxemia over a relatively short amount of time, typically a 2-3 month period.

Be Kind to your Gut 

You don’t have to feel overwhelmed & make big radical changes; small incremental changes over time will create profound effects on your microbiome. For example, adding 1 new type of food per week, 2-3 days a week of intermittent fasting, getting outside in a natural environment once a week, moving from regular to an organic version of your favorite food or personal care product, eating more polyphenols, adding in precision prebiotics or a spore-based probiotic; all these can have massive changes on your microbiome and shift you away from the path towards chronic illness. 

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