All disease begins in the gut.
This is not going to be a long post, something I’m sure many of you are grateful for;) But it is an extremely important one because what you learn today will serve as a foundation for many of the posts to come.
Endotoxemia is something I have been intensely studying because it promises to unravel the mystery behind what we commonly know as the diseases of civilization: type-two diabetes, obesity, liver disease, cardiovascular disease, etc.
This hypothesis postulates that the translocation of gram-negative bacteria and their cell-wall remnants from the gut is the proximate cause of the low-grade inflammatory response that underlie these metabolic disorders.
If true, then it would mean that preventing an overgrowth of these pathogens in the small intestine and colon and stopping them from crossing the gut wall into systemic circulation is the key to preventing these diseases.
Before I go any further, we need to revisit the cellular structure of gram-negative bacteria that I first explored in my post on plant lectins.
Gram-positive bacteria have a thick, exposed cellular wall called the peptidoglycan and it’s this part of the bacteria that retains a crystal-violet dye when stained in a laboratory therefore appearing blue under the microscope. Gram-negative bacteria, however, have a thin peptidoglycan layer sandwiched between an inner membrane and an outer membrane and it’s this outer membrane that can’t retain the dye or be agglutinated by lectins like wheat germ agglutinin.
It’s also this outer membrane that contains highly toxic components called endotoxins or lipopolysaccharides or LPS for short. LPSs are large molecules composed of both lipids and saccharides.
The facial hair that our threatening bacterial dude is sporting at the top of this post is a crude, albeit kind of cute, representation of LPS. But for the sake of accuracy, here is an actual illustration of the gram-negative bacterial cell wall:
Notice those hair-like structures extending from the outer membrane? Those are lipopolysaccharides. These molecules provoke powerful immune reactions in animals and humans. As inflammation is a necessary part of the immune response, whenever our immune system encounters lipopolysaccharides, inflammation always occurs.
A complex network of more than 100 signaling proteins called cytokines is engaged to marshal the resources of the immune system to fight them. Some cytokines you may have heard of include the interleukins, interferons and members of the tumor necrosis family.
What’s interesting about these LPSs is the fact that even after the gram-negative bacteria has been destroyed, these molecules still provoke an immune response. If enough of these remnants enter the blood, sepsis or blood poisoning is the result and the prognosis for recovery is not very good.
Inflammation is part of our immune response to threats. Without it, you would be defenseless against a whole host of pathogens. However, with inflammation comes the potential for damage to surrounding cells and tissues. This isn’t a real problem if the inflammatory response is limited in duration. The body is remarkably capable of healing whatever collateral damage was caused by an acute immune response.
An example of this is the common cold. That miserable feeling you experience is not caused by the cold virus, but by your immune system’s response to it. And raw, inflamed sinuses and nasal passages are the result. Once the cold is over, these mucosal surfaces heal and return to normal.
Not always so in chronic inflammation. Here the immune system continues to respond but for an extended period. In certain cases, even if the immune response ceases, the damage to surrounding tissue can be permanent and in the case of cancer initiation, potentially deadly.
What the theory of endotoxemia proposes is that the chronic inflammation that underlies many illnesses is provoked and sustained by these endotoxins. Where the inflammation manifests itself depends on where these LPS fragments end up. If in the liver, liver disease. If the arteries, cardiovascular disease. If the kidneys, kidney disease.
So the question that should be in the minds of those who have read this blog for any length of time is this: what are gram-negative bacteria doing in the small intestine and how is it possible that they are crossing the gut wall to gain access to systemic circulation?
The only species of bacteria that should colonize the small intestine are friendly gram-positive Lactobacillus.
As you recall from my small intestinal bacterial overgrowth (SIBO) series, the only reasons gram-negative bacteria have colonized your small intestine is:
- because there has been a breach in the stomach or gastric barrier defense or
- these pathogens have migrated from the colon because of impaired peristalsis or
- you are eating a diet that promotes either of the above two conditions or
- your beneficial small intestinal gut flora population is disordered or
- all the above.
So Ray, are you saying that those factors that predispose to SIBO can also predispose to these serious diseases as well?
Ding, ding, ding…..you win the Buick.
The next post will cover the role endotoxemia plays in the initiation of certain liver diseases.