Microbiome Detective: The World of Unseen Microbes
- Our ability to modulate the microbiome has been outsourced to microbes
- Faecalibacterium prausnitzii repairs our gut & low levels of it leads to inflammatory bowel disease
- LPS is the 'unknown villain' in your gut which can lead to diabetes, Alzheimer's & anxiety/depression
- Spore-based probiotics can blunt the endotoxin response from LPS & increase butyrate production by 50%
- Oligosaccharides can feed keystone species in our gut that protect us against several diseases
- The guts of hunter-gatherers & why fiber is critical for microbial diversity
- 'Precision Prebiotics' more than doubles the beneficial effects of spores
- C-reactive protein (CRP) is a cheap test for measuring gut inflammation
- Other markers for assessing gut health & inflammation
Outsourcing: Microbes do it Best
Compared to the past 10 years in microbiome research, the biggest difference that we currently have at our fingertips is Metagenomics, a sequencing technology that gives us an opportunity to study microbial DNA. It takes a lot of detective work & you need massive computing capability to look through all of that DNA. For example, our human DNA contains somewhere around 22,000 functional genes but bacterial DNA in our gut microbiome has over 2.5 million! It's a massive data stack & making sense of that data is really the hard but its a huge advancement that's given us insight into understanding this ecosystem.
On such insight is that, as a species, we have not developed any capability of modulating our own microbiome; we count on other microbes to be able to do that for us. We have a limited amount of genetic capability, barely enough as an earthworm, but what makes us sophisticated are the 2.5 million or so microbial genes in our system. In other words, being able to outsource functionality to microbes is a big part of being human. Through the course of evolution, there are sets of organisms that we have outsourced to modulate and monitor the rest of the microbiome and we're finding that when you start putting these microbes back, they start refereeing the ecosystem & making things more balanced & improved.
For example, you can completely turn over full lining of it your intestine within about 2-3 days but here's the most important aspect: it is dictated by the microbes that live there. One of the keystone species that's really well known for repairing & maintaining low inflammation in the gut lining is a bacteria called faecalibacterium prausnitzii. Those that have low levels of it tend to have much higher rates of inflammatory bowel disease such as Crohn's & Colitis. If you don't have it, at some point the damage overcomes the repair & you start getting significant inflammation of the gut lining. In summary, we're constantly battling this this state of damage & repair and it turns out that microbes are so so important for that.
LPS: The Unknown Villain
Another advancement in our understanding of the microbiome is that Lipopolysaccharides (LPS) are the the unknown villain in virtually everything. We all have LPS because its made by something called gram negative bacteria in our gut microbiome. When it's inside the bacteria it's not really an issue but every time a bacteria dies, it releases LPS. If allowed to leak through the lining of your gut and enter circulation, it's going to cause little mini nuclear bombs all throughout your body which is a big driver of aging.
There's a study that followed 490 prediabetic individuals over 60 months & measured all kinds of biomarkers to see which was the best predictor of going from prediabetes to diabetes; only the level of LPS in serum was predictive of going from prediabetes or diabetes. Another study published in 2017 showed that the foundation for the beta plaquing in the brains of Alzheimer's patients was gut-derived LPS & Alzheimer's patients tend to have high levels of LPS in the brain coming from the gut. If that weren't enough, LPS can also get into areas of the brain that that interrupt synaptic signaling, interfering with dopamine and serotonin binding which leads to depression & anxiety. It is the most pervasive endotoxin (made inside our bodies) that we have to deal with & it's mind-boggling how disruptive it is.
Spores: Taming the Offenders
When Microbiome Labs did their first clinical trial on LPS, they took individuals that had leaky gut and fed them things like a fast-food breakfast & microwave pizza and then measured their endotoxin level in circulation & all the inflammatory markers that come with it. What they saw is that subjects were profoundly affected by those foods & in some instances a single meal can profoundly increase their inflammatory response for up to two weeks. The question became: can their guts be fixed to a point where the same offending foods would no longer elicit an endotoxic response?
The premise was to add spore-based probiotics and then repeat the study. Spore-based probiotics (like Megaspore) have the capability of covering themselves in an armor-like coating and make it past stomach acid and & bile salts to enter the intestines. What they found was that in the majority of the group there was complete blunting of the endotoxic response although they were eating the same offending foods. They also saw a 50% increase in butyrate production, a postbiotic which is really important for healing the gut lining. Imagine if they were to take Megaspore while cleaned up their diet? It would do wonders for their gut.
Prebiotics: Precision Targeting
Probiotics need food to grow, but what do they like to eat the most?
Carbohydrates & Fiber.
Oligosaccharides are a unique type of carbohydrate because they were the first food for our microbiome; mother's milk contains 200 different types of these oligosaccharides. They are the quintessential prebiotic & many of them are highly complex where very limited groups of microbes can actually break them down. Oligosaccharides are called precision prebiotics because studies are showing that they specifically feed keystone species that have been shown to be protective against large categories of diseases:
- Faecalibacterium prausnitzii protects against everything under the inflammatory bowel disease spectrum.
- Akkermansia muciniphila protects against & is inversely correlated with metabolic syndrome.
- Bifidobacterium longum protects against cognitive-emotional damage to the brain.
Besides oligosaccharides, fiber's the part that's really going to move the needle on on the diversity in the gut. When we look at tribes in Papua New Guinea or the Hadza in Tanzania, they tend to have 3-4 times the microbial diversity of the western population and a lot of that comes from the roots and tubers that they eat. By adding in a good variety of fiber AND taking the Precision Prebiotic oligosaccharides, you're targeting the keystone species & doing more for your gut than the vast majority of people do. Microbiome Labs have confirmed that combining Precision Prebitoic (MegaPre) with MegaSpore more than doubles the effect of the spores.
Testing: Quantifying the Damage
How can your measure damage in your gut? Whatever's happening in your gut is impacting the blood in your circulation, and since gut dysfunction leads to inflammation, a cheap test that you can do is C-reactive protein (CRP) or high sensitivity CRP (hs-CRP). Going further, once LPS is in your system it elevates key cytokines & the 3 surrogate markers for LPS damage in the body are Interleukin 6 (IL-6), Interleukin 1 beta (IL-1β) & soluble CD14 (sCD14). If you do any of those, you're getting a clue into the cellular-level inflammatory damage that's occurring in your body. On a final note, it's interesting to mention that in one study conducted to predict the most severe responses to the current pandemic, it was found that those with high IL-6 had higher risk for hospitalization & even death so its an important biomarker to watch out for.
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