(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
It’s a challenge to find an appropriate place to introduce the microbiome in a discussion where you’re trying to develop an evolving narrative of the immune system. As you will see, it is so intimately involved in so many aspects of the system that you can introduce it in a dozen places. The slightly silly subtitle I added, "gut-axis-du jour," ain't so silly when you follow the microbiome research and literature. I used more than 2400 words discussing it in my "Paradox of the Immune System" book and that only "tree-topped" it up to June 2022. Not a week goes by that there isn't another update on the microbiome,
What we’ll do in this brief discussion is introduce its basic elements and then expand on its relevance in subsequent blog discussions as it keeps resurfacing and applies as an important feature in so many immune topics. And, it works well to start here, just after our genetics and genomics discussion back in Blog #10 because the microbiome is referred to as “the second genome” of the human body.
Starting with a little trivia about the microbiome, there are more bacteria in our body (greater than 30 trillion) than there are human cells with an estimate of approximately 57% of our cells actually being a mixture of microbes and 43% human cells. It is this enormous array of microbiota, aka microorganisms found in a particular habitat, in this case our body, that makes it “the second genome.” The unique difference in the human versus the microbial genome is their evolutionary development. Whereas the DNA of the human genome is very stable allowing for predictable heredity with only slight mutations over time, sometimes over millions of years, the microbial “second genome” changes far more frequently. As a matter of fact, the only time it is predictable is at birth. That is when the newborn will inherit some microbes from the mother described in Blog #8. As we described, this is a critical process that allows the baby to begin to deal with pathogens outside of the womb. The transfer of microbes to the newborn happens during vaginal births when the baby is exposed to the mother’s gut and vaginal microbes during delivery. This triggers the baby’s immune system, allowing for early protection and more so, a better ability to absorb nutrients from the mother’s breast milk.
Everything in this world is covered by microbes, so obviously we are constantly inhaling and ingesting microbes and creating our own gut microbiota. And so, the theory is that the constant 24/7 exposure of gut microbes to immune cells, from birth on creates a state of chronic, albeit subclinical (most of the time), inflammation in our gastrointestinal (GI or gut) system from oral to colorectal syndromes. This chronic state produces a “symbiosis” or a “biological synergy” of “peaceful and complementary coexistence” between immune cells and the microbes. Such a biological synergy includes fighting off invading microorganisms like pathogens, thanks to that great antibody-encoding gene we’ve mentioned and described a number of times as part of our human genome. Our immune system has an almost infinite array of antibodies to achieve this goal, but because of the enormity of the task, it looks like we have evolutionarily come to enlist help from “normal flora” microbes or “the microbiome.” No doubt, an imbalance of this powerful microbiome can produce serious health consequences.
The microbiome also involves yet another specialized subset of the T cells that we have mentioned previous, and a rather powerful T cell at that. As discussed previously in Blog #5, it is the T regulatory cell or Treg, also referred to as the T suppressor or Ts cell. One of its functions is to suppress the immune system when it becomes too overactive and dysregulated. It has been shown that bacteria from the microbiome trigger Treg cells (and other killer immune cells like natural killer cells [NKs] and T cytotoxic [TC] cells). This causes the microbiome to become a mitigating force against inflammation, autoimmune disease, and even cancers as it modulates the immune system. Human’s inherent desire to “clean” everything, called the “hygiene hypothesis” suggests that we may be compromising our microbiome. Could this be a cause of increasing autoimmune diseases and some cancers? And regarding cancers and the microbiome, distinct aspects of the microbiota have been reported to have either pro- or antitumor effects. Thus, modulating the microbiome in certain individuals could also have implications for cancer prevention. More on this in Blog #29.
This is the last blog discussion related to “Our friendly immune system” or Section 1 of the book, “The Paradox of the Immune System.” Section 2, entitled “The enemy within us” will deal with the darker side of immunology. To wit, I used a “strained” metaphor in the book which I’ll try here as well. “Having paid a peaceful, relatively untroubled visit to “our friend,” the regulated immune system in Section 1, now it’s time to visit the darker, far less pleasant side of immunity, the “dysregulated” immune system. I’m afraid “we’re not in Kansas anymore, Toto. It’s time to ‘look behind the curtain’.” Sorry about that.
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