Cancer: An Odyssey Part 5: Gut Microbiome & Immune Defense, The Greater Ajax
“Be men now, dear friends, remember your furious valour. Do we think there are others who stand behind us to help us? Have we some stronger wall that can rescue men from perdition. We have no city built strong with towers lying near us, within which we could defend ourselves and hold off this host that matches us... Salvation's light is in our hands' work, not the mercy of battle”
— Greater Ajax, The Iliad
We now move into Part 5 of our journey having discussed several of the important factors in attacking the cancer. We laid out how to besiege it by starving it and beating it from the inside out in Parts 2 & 3, whereas in Part 4, we discussed how to lay down a more direct attack.
But what about our own internal defense system?
As the Greater Ajax asked his compatriots, “have we some stronger wall that can rescue men from perdition?”
Well, we do have this wall, our innate immune system centered around our, wait for it: gut microbiome!
In fact, roughly 70-80% of our bodies immune cells are found in the gut [1].
Unfortunately, the majority of us, particularly those afflicted by cancer, have the unholy trinity of intestinal permeability (leaky gut), gut dysbiosis and subsequent immune dysregulation.
Immune dysregulation is a hallmark of many diseases and presents in essentially 4 different categories: under- or overactive responses to external or internal stimuli [2].
Overactive responses to external stimuli result in allergies and food/environmental sensitivities, whereas when it is to an internal stimulus, autoimmune conditions can result. Conversely, an insufficient response to an external stimulus can result in viral or microbial infection and to an internal stimulus is a major issue in the development and proliferation of cancer [2].
It is important to note, however, that these categories are not mutually exclusive insomuch as once immune dysregulation is established; you can become more susceptible to the other types of reactions [3].
That being said, modulators immunotherapy is the next frontier in treatment within the conventional paradigm, which may finally result in the death of the current Big 3 of chemotherapy, radiation and surgery [4; 5].
Unfortunately, as addressed on Part 1, the Big 3 modalities act like nuclear warfare, destroying everything, including the immune system, and hoping the body can recover from the fallout. However, recent advances are attempting to use immunotherapy as an adjunct to help foster the recovery process [5, 6, 7].
But, just as the world has generally agreed to shelf the production and use of nuclear arms, wouldn't it be more prudent to do the same to the Big 3?
“If you try to cure evil with evil, you will add more pain to your fate.”
— Sophocles, Ajax
Well, fortunately, such a plan is already in place and at its core is modulation of our biological brothers in our gut microbiome. Supporting the microbiome will result in an improved and appropriate immune response to cancer [8, 9, 10].
Unfortunately, as we established, gut dysbiosis can play an immensely important role in the development and progression of cancer [11, 12].
There are a number of mechanisms by which this occurs, but a primary culprit is the endotoxin lipopolysaccharide (LPS), found in the cell membrane of gram-negative bacteria [12, 13, 14, 15]. Lipopolysaccharides are a potent mediator of inflammation and activate the toll-like receptor (TLR), which can drive the inflammatory response [12, 13].
Additionally, LPS is able to induce metastasis, by way of increased angiogenesis and vascular permeability, through increasing nitric oxide synthase [14]. If that weren't enough, LPS can also activate the much maligned PI3K/Akt pathway, that we have discussed in pretty much every part of this series, resulting in the metabolic shift of cancer cells to aerobic respiration [16, 17].
Now, normally bacteria are found predominantly in the gut; however, damage to the epithelial cell and mucosal walls can result in bacterial translocation into the bloodstream, subsequently releasing LPS and other endotoxins, leading to other organ and systemic inflammation [18].
But what causes damage to the wall that is supposed to protect us?
Well, unfortunately, that list is quite extensive and a full exploration is beyond the scope of this article. However, the “short” list of the biggest offenders are those pathogenic bacteria and the endotoxins they produce, as well as the resultant inflammation [19, 20], pharmaceutical drugs including chemotherapy [20, 21, 22], psychological and emotional stress [23, 24] and poor diet [25, 26, 27].
Regarding microflora diversity, not only does TLR activation by pathogenic bacteria damage epithelial and mucosal walls, but the presence of commensal bacteria actually is essential for their proper maintenance by TLR, as well [20, 28, 29]. Once again establishing the importance of having the appropriate bacteria in your gut.
So how do we do that?
Well the first, obvious step is for the inclusion of probiotic supplementation and fermented foods. Probiotics have shown efficacy in repairing the gastrointestinal walls [24, 30, 31], regulating the immune system [32, 33] and simply in improving cancer prognosis [34, 35], particularly during concurrent chemotherapy and/or radiation treatment [36].
Unfortunately, often times probiotic bacteria are unable to survive the transit through the gastrointestinal tract and contribute to the diversity of the microflora [37, 38, 39].
As such, that is why we are using MegaSporeBiotic, insomuch as spore-based probiotics are more resistant to heat and the acidic conditions encountered in the stomach and do not germinate, or become active, until they reach their proper location in the large intestine [40, 41, 42].
Moreover, these strains have shown efficacy at restoring the epithelial barrier, modulating immune function and in the process of endogenous vitamin production [43, 44, 45]. They also have a demonstrated antimicrobial effect against Clostridium difficile [46], a pathogen that commonly infects cancer patients through the use of chemotherapy, radiation and antibiotics [47].
If that weren't enough, in a teaser for Part 6, Bacillus subtilis also produces nattokinase, a potent systemic enzyme that can improve circulation through its fibrinolytic activity (the ability to breakdown fibrin blood clots) [48].
Moving forward with ways to support gut health and subsequent immune function are dietary choices. Again, full discussion is beyond the scope of this article; however, some important inclusions are cruciferous vegetables, rich in potent phytochemicals and dietary fiber, which the gut bacteria can then ferment into short chain fatty acids, butyrate in particular [49, 50].
Butyrate is essential for the proper functioning of the intestinal epithelial cells, improves immune regulation and insulin sensitivity, and has even been shown to induce apoptosis in cancer cells [49, 51, 52, 53]. Full-fat, organic, grass-fed dairy is another excellent source of butyrate (named after the Latin word for butter) [51].
The biggest foods to avoid are refined sugars and grains, particularly wheat.
Sugar plays a role in feeding opportunistic, pathogenic bacteria [54], as well as the cancer cells, which we have already discussed ad nauseam. Whereas wheat is associated with increased intestinal permeability, due to its effect on zonulin, a protein that regulates the tight junctions of the intestinal wall [25, 54, 55].
However, some in particular to note are turmeric, and one of its active constituents, curcumin, which improves intestinal barrier integrity and reduces inflammation [56, 57]. This is one of the many reasons Synchro Gold is a major component of my father's protocol.
Bromelain is another systemic enzyme, which apart from its circulation, anti-inflammation and direct anti-cancer benefits, modulates the immune system and exhibits anti-microbial action against intestinal pathogens [58]. This, along with the previously discussed nattokinase, are key ingredients in Fibrenza, which we will be investigating more in Part 6.
The final interesting immunomodulatory therapies are by way of hyperoxic and hyperthermic exposure.
Hyperoxic therapy, as discussed in Part 3, has been shown to promote and enhance the immune system [59].
The induction of hyperthermia can also enhance the immune system, particularly through the release of heat-shock proteins [60].
This is a major reason why, as soon as we have him walking again, my father will be over at LaFlare Skin Care inside of Long Island MMA for regular sauna usage.
That being said, I really had to constrain myself with this article to not get dragged too deep down the rabbit hole. The knowledge and appreciation of the relationship between our gut microbiome and disease, particularly cancer, is ever expanding.
Greater Ajax perfectly represents our innate immune system as governed by our gut microbiome. He was one of the most powerful warrior in the Greek army, second only to Achilles (or in our analogy targeted oxidative stress).
Moreover, he died by his own hands in shame after being tricked into attacking the wrong thing. Similarly, gut dysbiosis can induce immune dysregulation, which tricks our bodies into not attacking the cancer cells.
An improperly functioning immune system can cause the body to mistake itself for an enemy or the enemy for a friend, which makes it critical to ensure that our gut homeostasis.
“Shall not I learn place and wisdom? Have I not learned this, only so much to hate my enemy, as though he might again become my friend, and so much good to wish to do my friend, as knowing he may yet become my foe?”
— Greater Ajax, Ajax
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