“Be a free thinker and don’t accept everything you hear as truth. Be critical and evaluate what you believe in.”
Metabolic endotoxemia is not some opinion or loose theory, and it has strong support in scientific evidence. The connection between metabolic endotoxemia, metabolic dysfunction, and dis-aise is not just one of association but causation. As I have discussed previously, chronic inflammation, triggered in metabolic endotoxemia, has been shown to contribute to an outright cause:
- Insulin resistance
- Cardiovascular disease
- Autoimmune diseases
- Psychiatric diseases
- Neurodegenerative diseases
It would be hard to find any individual or family that is untouched by this list today. Poor health and disease are rampant today. Despite the billions of dollars and investments in new technology spent over the last many decades, the number of people affected by poor health and disease only continues to grow. Why could this be? How could this be? Maybe it is because the medical community is more reactive instead of proactive. Maybe, it is because the medical community focuses on waiting for disease instead of acting to prevent disease.
Suppose you don’t take anything from this series on the diet, gut, metabolic endotoxemia, and disease connection. In that case, I hope that I have shown that poor health begins through diet and in the gut and moves systemically through the body in what is called metabolic endotoxemia. In direct contrast, the beginning of a return to healing and wellness begins in the same diet, gut connection.
The list above can seem categorically disconnected to individual experience. You may not be struggling with obesity or any other listed disease. You may be twenty-four years of age, in the best health of your young life, and see no relevance to discuss any such disease; because, of course, you will live forever. Disease is not a concern until it is, and the value of wellness is only known when it is lost. You may struggle with or have personal experience with one of the named diseases on this list, but why concern yourself with all of them. Not for fear, but for personal empowerment, let me make the connection extremely relevant and applicable to all people via current events. Of course, the emphasis and focus will be on those with cancer or at risk of cancer.
Unless you have been living on another planet in the last year and a half, you may be aware of a particular virus that the entire world has been dealing with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has been implicated in the harm and death of many people worldwide. The people at most risks from the SARS-CoV-2 virus are those that have coexisting comorbidities. These comorbidities include advancing age, obesity, male > female, cardiovascular disease, and diabetes.
Metabolic endotoxemia and SARS-CoV-2
So, what is the connection to metabolic endotoxemia?
A December 2020 article in the Journal of Molecular Cell Biology, “SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity” , helps to provide the connection between SARS-CoV-2 and metabolic endotoxemia? I have spent several blog posts highlighting the clear link between systemic LPS, metabolic endotoxemia, and insulin resistance, inflammation, metabolic syndrome, obesity, diabetes, cardiovascular disease, autoimmune disease, and cancer. All are comorbidities associated with SARS-CoV-2, and as a result, there is an increased risk of severe illness with SARS-CoV-2. They are different yet connected. The direct point here is that gut dysbiosis is the origin of the LPS induced systemic inflammatory (metabolic endotoxemia) response that sets the stage for severe illness and disease–comorbidities. Worse, in a global pandemic from a new coronavirus, LPS induced metabolic endotoxemia causes the comorbidities that set the stage for worse outcomes from SARS-CoV2 infection. Without metabolic endotoxemia and the other comorbidities, where is the risk from this new novel coronavirus? Your health is important in preventing the known and the still yet unknown, like a novel virus.
Oh, but it gets much more profound. This connection is not theory but is according to the available published research. Not only does LPS set the start for the comorbidities that increase the risk associated with SARS-CoV-2 infection, Gianna Petruk and colleagues show that LPS works synergistically with the spike protein from the SARS-CoV-2 virus to further increase inflammation through an increase in nuclear factor-κB (NF-κB) transcription, activation, and pro-longed signaling. Each alone, SARS-CoV-2 infection or LPS metabolic endotoxemia, can create problems, but collectively, cause significantly more systemic havoc through pro-longed nuclear factor-κB (NF-κB) transcription.
What exactly is NF-κB? Nuclear factor-κB is a protein complex that serves as a key transcription factor in inflammation. It is found in all nucleated cells in the body and is one of the primary regulatory signals in inflammatory signaling within the body. Together with the SARS-CoV-2 virus increases systemic inflammation, cytokine storm, complications, and mortality risk .
It is essential to connect a few dots to bring cancer into this relationship. More than just the SARS-CoV-2 infection, an increase in NF-κB transcription signaling is the link between inflammation and cancer. It is the line of differentiation between normal function and abnormal function, or wellness and disease.
A publication from 2002 first suggested the link between NF-κB transcription and cancer . Broadly, an increase in NF-κB activation and signaling is associated with an increase in cancer development, progression, and metastasis. Specifically, NF-κB plays a role in:
- Carcinogenesis   
- Malignant transformation  
- Oncogenic metabolism   
- Alters the Tumor Microenvironment (TME) 
- Prevents apoptosis (programmed cell death) 
- Promotes angiogenesis  
- Promotes proliferation 
- Promotes invasion 
- Promotes immune evasion and escape  
- Promotes Epithelial to Mesenchymal Transition (EMT)    
- Promotes metastasis 11  
- Chemoresistance  
- Radiation resistance   
I will say what appears to be the obvious, nuclear factor-κB (NF-κB) transcription sits at the heart of many processes critical to cancer.
If more proof is required, NF-κB is at the center of promoting cancer cell stem (CSC) activity, treatment resistance, and ultimately metastasis    . Cancer stem cells are the cancer backups that play a pivotal role in treatment resistance and recurrence. It is the backup that nobody wants any part of. A computer backup or phone backup can be life-saving in terms of data and frustration, but cancer cell backups (CSC) literally take lives. Whether with chemotherapy or radiation, which is often the result of CSC activity, treatment resistance is vital in treatment failure, morbidity, and mortality.
The important take-home points here are that metabolic endotoxemia (LPS) alone sets the stage for obesity, metabolic syndrome, diabetes, cardiovascular disease, neurodegenerative disease, and many other chronic diseases of aging. In the new era of SARS-CoV-2, these diseases are also known as comorbidities. Whether in disease or as a comorbidity, LPS plays a critical role. SARS-CoV-2 is the new coronavirus that creates problems alone in those with the same pre-existing comorbidities. However, in conjunction with systemic LPS through metabolic endotoxemia, the combination imparts more risk and damage than either individually. The fireworks here are provided by NF-κB, augmented by LPS, and it plays a vital role in the cancer process.
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